Four levels of protein structure
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Jul 03, 2019
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About This Presentation
A comprehensive presentation on Four levels of protein structure for MBBS, BDS, B Pharm & Biotechnology students to facilitate self- study.
Slide Content
Four levels of protein structure
Dr. Rohini C Sane
Dr. Rohini C Sane
Structure of proteins
❖Proteins are polymers of amino acids and made up of one or more
polypeptide chains .
❖Every protein in its native state has a unique three dimensional
structure which is referred to as its conformation.
❖The number and sequence of these amino acids in the protein are
different in different proteins.
❖The function of a protein arises from its conformation.
❖Protein structure can be classified into four levels of organization.
❖Proteins are polymers of amino acids and made up of one or more
polypeptide chains .
❖Every protein in its native state has a unique three dimensional
structure which is referred to as its conformation.
❖The number and sequence of these amino acids in the protein are
different in different proteins.
❖The function of a protein arises from its conformation.
❖Protein structure can be classified into four levels of organization.
Configuration and Conformation of a molecule
Configuration of
compound
denotes the spatial
relationship between
particular atoms
e.g. L-amino acids
and D-amino acids
Conformation of
molecule
means the spatial
relationship of every
atom in a molecule
e.g. rotation of a
portion of the
molecule
Configuration of
compound
denotes the spatial
relationship between
particular atoms
e.g. L-amino acids
and D-amino acids
Conformation of
molecule
means the spatial
relationship of every
atom in a molecule
e.g. rotation of a
portion of the
molecule
Four levels of protein structure
Proteins are the polymers of L--amino acids. The structure of proteins is rather complex
which can be divided into four levels of organization.
Proteins: polypeptide with more than 50 amino acid residues
Proteins are the polymers of L--amino acids. The structure of proteins is rather complex
which can be divided into four levels of organization.
Proteins: polypeptide with more than 50 amino acid residues
Four levels of structural organization of proteins
❖Proteins are polymers of amino acids and made up of one or more
polypeptide chains .
❖Four levels of structural organization can be recognized in proteins:
1.Primarystructure: is determined by the number and sequence of amino
acids in the protein.
2.Secondary Structures: is the conformation of polypeptide chain formed
by twisting or folding . It occurs when amino acids are linked by hydrogen
bonds to form -helix and -sheets .
3.Tertiary Structure: is the three dimensional arrangement of protein
structure. It is formed when alpha-helices and beta-sheets are held
together by weak interactions.
4.Quaternary structure: occurs in protein(oligomers) consisting of more
than one polypeptide chain where certain polypeptides aggregate to
form one functional protein.
❖Proteins are polymers of amino acids and made up of one or more
polypeptide chains .
❖Four levels of structural organization can be recognized in proteins:
1.Primarystructure: is determined by the number and sequence of amino
acids in the protein.
2.Secondary Structures: is the conformation of polypeptide chain formed
by twisting or folding . It occurs when amino acids are linked by hydrogen
bonds to form -helix and -sheets .
3.Tertiary Structure: is the three dimensional arrangement of protein
structure. It is formed when alpha-helices and beta-sheets are held
together by weak interactions.
4.Quaternary structure: occurs in protein(oligomers) consisting of more
than one polypeptide chain where certain polypeptides aggregate to
form one functional protein.
Four orders ofprotein Structure
Primarystructure is determined
by the sequence of amino acids.
Secondary Structures:the
number and sequence of amino
acids in the protein. It occur
when amino acids are linked by
hydrogen bonds to form -helix
and -sheets .
Tertiary Structure: is the three-
dimensional arrangement of protein
structure.
Quaternary structure: occurs in protein(oligomers)
consisting of more than one polypeptide chain where certain
polypeptides aggregate to form one functional protein.
Primarystructure is determined
by the sequence of amino acids.
Secondary Structures:the
number and sequence of amino
acids in the protein. It occur
when amino acids are linked by
hydrogen bonds to form -helix
and -sheets .
Tertiary Structure: is the three-
dimensional arrangement of protein
structure.
Quaternary structure: occurs in protein(oligomers)
consisting of more than one polypeptide chain where certain
polypeptides aggregate to form one functional protein.
Four
orders of
protein
structure:
Bricks
Wall
Rooms
Building
Aminoacids
(Bricks )
Secondary structure
(bends /twist in walls)
Tertiary structure (self –contained room)
Primary structure
(walls)
Quaternary structure(building with similar/dissimilar rooms
StructuralHierarchy
of proteins
orders of
protein
structure:
Bricks
Wall
Rooms
Building
Aminoacids
(Bricks )
Secondary structure
(bends /twist in walls)
Tertiary structure (self –contained room)
Primary structure
(walls)
Quaternary structure(building with similar/dissimilar rooms
StructuralHierarchy
of proteins
Structuralhierarchy of proteins
•Primarystructure: isalinear sequence of amino acids forming a backbone of
proteins .Itrefers to the order in which amino acids are linked together in the
peptide chain. e.g. Glutathione: Tripeptide : Glutamicacid-Cysteine-Glycine
Methionine Enkephalins:pentapeptide:Try-Gly-Gly-Phe-Met
•(N-terminal end) →H
2N --COOH(C-terminal end)
•Peptide bond →linear , planner ,rigid ,partial double bond character
❖SecondaryStructures:spatial arrangement of proteins by twisting of
polypeptide chain= folding patterns in proteins (alpha-helix ,beta-sheet )
❖TertiaryStructure: Three dimensional structure generated by interaction
between the amino acid residues of functional proteins.
❖Quaternary structure : refers to the spatial arrangement of subunits of
proteins which are joined by non-covalent interactions . This is seen in proteins
with two or more polypeptides chains(oligomers).
❖Super secondaryStructures:indicate folding patterns in proteins
•Primarystructure: isalinear sequence of amino acids forming a backbone of
proteins .Itrefers to the order in which amino acids are linked together in the
peptide chain. e.g. Glutathione: Tripeptide : Glutamicacid-Cysteine-Glycine
Methionine Enkephalins:pentapeptide:Try-Gly-Gly-Phe-Met
•(N-terminal end) →H
2N --COOH(C-terminal end)
•Peptide bond →linear , planner ,rigid ,partial double bond character
❖SecondaryStructures:spatial arrangement of proteins by twisting of
polypeptide chain= folding patterns in proteins (alpha-helix ,beta-sheet )
❖TertiaryStructure: Three dimensional structure generated by interaction
between the amino acid residues of functional proteins.
❖Quaternary structure : refers to the spatial arrangement of subunits of
proteins which are joined by non-covalent interactions . This is seen in proteins
with two or more polypeptides chains(oligomers).
❖Super secondaryStructures:indicate folding patterns in proteins
Primarystructure of proteins
•Primarystructure of proteins denotesthenumberandsequenceof amino acids in protein.
Thesuccessiveaminoacidsarelinkedby peptide bond(covalent bond).
•Generally ,amino acids are arranged as a linearchain. Each component amino acid is
called a residueor moiety. Very rarely, proteins may be a branched form or circularform
(Gramicidin) . Primary structure of proteins is largely responsible for its functions.
•The branching points in the polypeptide chain may be produced by interchain disulphide
bridges (the covalent disulphide bonds between different polypeptide chains in the same
protein) or portion of the same polypeptide chain (intrachain). They are part of primary
structure.
•Each polypeptide will have an amino terminal ( N-terminal ) with free amino group and a carboxy terminal
ends ( C-terminal) with free carboxy group . By convention, they are represented with amino
terminalon the leftand carboxyterminalend on the rightend.
•The amino acids composition of protein determines its physicaland chemicalproperties.
•Primary structure of proteins (sequenceof amino acids ) is determined by the genes contained in DNA.
Primary structure of number of proteins are known today . e.g. Insulin, Glucagon , Ribonuclease , Growth
hormones. AnychangeinthePrimarystructureof proteins affecttheir functions.
•Primarystructure of proteins denotesthenumberandsequenceof amino acids in protein.
Thesuccessiveaminoacidsarelinkedby peptide bond(covalent bond).
•Generally ,amino acids are arranged as a linearchain. Each component amino acid is
called a residueor moiety. Very rarely, proteins may be a branched form or circularform
(Gramicidin) . Primary structure of proteins is largely responsible for its functions.
•The branching points in the polypeptide chain may be produced by interchain disulphide
bridges (the covalent disulphide bonds between different polypeptide chains in the same
protein) or portion of the same polypeptide chain (intrachain). They are part of primary
structure.
•Each polypeptide will have an amino terminal ( N-terminal ) with free amino group and a carboxy terminal
ends ( C-terminal) with free carboxy group . By convention, they are represented with amino
terminalon the leftand carboxyterminalend on the rightend.
•The amino acids composition of protein determines its physicaland chemicalproperties.
•Primary structure of proteins (sequenceof amino acids ) is determined by the genes contained in DNA.
Primary structure of number of proteins are known today . e.g. Insulin, Glucagon , Ribonuclease , Growth
hormones. AnychangeinthePrimarystructureof proteins affecttheir functions.
Peptide bond formation
•Formation of peptide bond = a
covalent bond is formed by amide
linkage between the -carboxyl
group of one amino acid and -
amino group of another amino acid
by removal of a water molecule.
•Successive amino acids are
joined/cemented by peptide bond
( -CO-NH) in proteins .
➢The peptide bonds form strong
backbone of polypeptide and side
chains of amino acid residue project
outside the peptide backbone.
Dipeptide :two amino acids and one peptide bond ( not two bonds)
•Formation of peptide bond = a
covalent bond is formed by amide
linkage between the -carboxyl
group of one amino acid and -
amino group of another amino acid
by removal of a water molecule.
•Successive amino acids are
joined/cemented by peptide bond
( -CO-NH) in proteins .
➢The peptide bonds form strong
backbone of polypeptide and side
chains of amino acid residue project
outside the peptide backbone.
Dipeptide :two amino acids and one peptide bond ( not two bonds)
CharacteristicsofPrimarystructure of proteins:1
1.A peptide contains two or more amino acid residues joined together by a peptide bonds. Individual amino
acids can be considered as bricks .
2.Formation of peptide bond = a covalent bond is formed by amide linkage between the -amino group of
one amino acid and -carboxyl group of another amino acid by removal of a water molecule.
3.Characteristics of a Peptide bond:
a.Rigid ,covalent, stable, strongand can be hydrolyzed by the action of proteolytic enzymes, acids and
alkalis
b.Planer and with partial double bond (no freedom of rotation) in character
c.–C=O ,NH –Exist in trans-configuration .Both groups are polar and involved in hydrogen bonds.
d.Impart stability to the primary structure of proteins(disulphide bonds are also responsible for the stability)
e.The side chain are free to rotate on either side of the peptide bond.
f.Distance between amino acids is 1.32 Awhich is midway between that of single bond (1.49 A) and
double bond ( 1.27A)
g.Ramachandranangles: are angle of rotation →determine the spatial orientation of peptide chain
1.A peptide contains two or more amino acid residues joined together by a peptide bonds. Individual amino
acids can be considered as bricks .
2.Formation of peptide bond = a covalent bond is formed by amide linkage between the -amino group of
one amino acid and -carboxyl group of another amino acid by removal of a water molecule.
3.Characteristics of a Peptide bond:
a.Rigid ,covalent, stable, strongand can be hydrolyzed by the action of proteolytic enzymes, acids and
alkalis
b.Planer and with partial double bond (no freedom of rotation) in character
c.–C=O ,NH –Exist in trans-configuration .Both groups are polar and involved in hydrogen bonds.
d.Impart stability to the primary structure of proteins(disulphide bonds are also responsible for the stability)
e.The side chain are free to rotate on either side of the peptide bond.
f.Distance between amino acids is 1.32 Awhich is midway between that of single bond (1.49 A) and
double bond ( 1.27A)
g.Ramachandranangles: are angle of rotation →determine the spatial orientation of peptide chain
CharacteristicsofPrimarystructure of proteins:2
5.Inpolypeptidechain, at one end there will be one free alpha amino group→N-
terminal end and protein biosynthesis starts from amino terminal end (the first
amino acid ).
6.The other end of polypeptidechain, is carboxy terminal end (the last amino acid)
where there is free alpha carboxygroup.
7.All other alpha-amino acids and alpha-carboxygroups are involved in peptide bond
formation.
8.Writing of peptide structures–by convention ,the amino acid sequence is written
from left to right with the free amino end (N-terminal acid/residue→number 1 by
tradition) on left and ending with the free carboxyl end (C –terminal amino acid /
residue).
9.Shorthand to read peptides : three letter or oneletter abbreviation/ short hand
form of amino acids in protein to be read from N-terminal residue on leftof
peptide e.g. (Gly-Ala–Val)→Glycyl –Alanyl –Valine →G A V
Or NH
2-Gly-Ala-Val-COOH
10. Namingpeptides: for naming peptides the amino acid Suffixesine(Glycine →to
glycyl) , an(Tryptophan), ate( Glutamate→Glutamyl) by ylwith the exception of C-
terminal amino acid.
5.Inpolypeptidechain, at one end there will be one free alpha amino group→N-
terminal end and protein biosynthesis starts from amino terminal end (the first
amino acid ).
6.The other end of polypeptidechain, is carboxy terminal end (the last amino acid)
where there is free alpha carboxygroup.
7.All other alpha-amino acids and alpha-carboxygroups are involved in peptide bond
formation.
8.Writing of peptide structures–by convention ,the amino acid sequence is written
from left to right with the free amino end (N-terminal acid/residue→number 1 by
tradition) on left and ending with the free carboxyl end (C –terminal amino acid /
residue).
9.Shorthand to read peptides : three letter or oneletter abbreviation/ short hand
form of amino acids in protein to be read from N-terminal residue on leftof
peptide e.g. (Gly-Ala–Val)→Glycyl –Alanyl –Valine →G A V
Or NH
2-Gly-Ala-Val-COOH
10. Namingpeptides: for naming peptides the amino acid Suffixesine(Glycine →to
glycyl) , an(Tryptophan), ate( Glutamate→Glutamyl) by ylwith the exception of C-
terminal amino acid.
Use of symbols in representing a peptide
•A tripeptide →3 amino acids and 2 peptide bonds is shown.
H
3 N
+
Glutamate–Cysteine–Glycine-COO
-
E – C –G
Glu – Cys–Gly
Glutamyl–cysteinyl–Glycine
•Free amino end (N-terminal acid/residue) →-N
+
H
3is on the left.
Free carboxyl end (C –terminal amino acid / residue)→-COO
-
is on right .
•The amino acid sequence is written and read from left to right. This is the
chemical shorthand to write proteins.
one letter abbreviation
three letter abbreviation
Peptide name
Amino acids in a peptide
•A tripeptide →3 amino acids and 2 peptide bonds is shown.
H
3 N
+
Glutamate–Cysteine–Glycine-COO
-
E – C –G
Glu – Cys–Gly
Glutamyl–cysteinyl–Glycine
•Free amino end (N-terminal acid/residue) →-N
+
H
3is on the left.
Free carboxyl end (C –terminal amino acid / residue)→-COO
-
is on right .
•The amino acid sequence is written and read from left to right. This is the
chemical shorthand to write proteins.
one letter abbreviation
three letter abbreviation
Peptide name
Amino acids in a peptide
Polypeptide chain showing N-terminal and C-terminal
•Schematic diagram
NH
3
+
–CH–CO–NH–CH–CO–NH–CH–CO–NH–CH–CO–NH-CH–COO
-
I I I I I
R
1
R
2
R
3
R
4
R
5
N-terminal
peptidebond amino acid residue
C -terminal
N C
•Schematic diagram
NH
3
+
–CH–CO–NH–CH–CO–NH–CH–CO–NH–CH–CO–NH-CH–COO
-
I I I I I
R
1
R
2
R
3
R
4
R
5
N-terminal
peptidebond amino acid residue
C -terminal
N C
Aminoacid Aminoacid
composition
of Human
CytochromeC
(1 04 AA)
Aminoacid
compositionof
Bovine
Chymotrypsinogen
(245AA)
Ala 6 22
Arg 2 4
Asn 5 15
Asp 3 8
Cys 2 10
Glu 8 5
Gln 2 10
Gly 13 23
His 3 2
Ile 8 10
Aminoacid Aminoacid
compositionof
Human
CytochromeC
(1 04 AA)
Aminoacid
compositionof
Bovine
chymotrypsinogen
(245AA)
Leu 6 19
Lys 18 14
Met 3 2
Phe 3 6
Pro 4 9
Ser 2 28
Thr 7 23
Trp 1 8
Tyr 5 4
Val 3 23
composition
of Human
CytochromeC
(1 04 AA)
Aminoacid
compositionof
Bovine
Chymotrypsinogen
(245AA)
Ala 6 22
Arg 2 4
Asn 5 15
Asp 3 8
Cys 2 10
Glu 8 5
Gln 2 10
Gly 13 23
His 3 2
Ile 8 10
Aminoacid Aminoacid
compositionof
Human
CytochromeC
(1 04 AA)
Aminoacid
compositionof
Bovine
chymotrypsinogen
(245AA)
Leu 6 19
Lys 18 14
Met 3 2
Phe 3 6
Pro 4 9
Ser 2 28
Thr 7 23
Trp 1 8
Tyr 5 4
Val 3 23
Clinical applications of primary structure
❖Clinical applications of primary structure :
1.Presence of specific amino acid at a specific position/number is very
significant for a particular function of protein . Any change in the
sequence is abnormal and may affect the functions and properties
of proteins .
2.Many geneticdiseasesresult from protein with abnormalamino
acidsequences. If the primary structureofthenormaland
mutatedproteins are known ,the this information may be used to
diagnoseor clinical study of the disease.
❖Clinical applications of primary structure :
1.Presence of specific amino acid at a specific position/number is very
significant for a particular function of protein . Any change in the
sequence is abnormal and may affect the functions and properties
of proteins .
2.Many geneticdiseasesresult from protein with abnormalamino
acidsequences. If the primary structureofthenormaland
mutatedproteins are known ,the this information may be used to
diagnoseor clinical study of the disease.
Secondarystructure of proteins
3 dimensional Conformation of the
polypeptide chain bytwistingor
foldingis referred to as a secondary
structure.
(Types :Alpha-helix ,Beta-pleated sheet)
3 dimensional Conformation of the
polypeptide chain bytwistingor
foldingis referred to as a secondary
structure.
(Types :Alpha-helix ,Beta-pleated sheet)
SecondaryStructures of proteins
•SecondaryStructures:spatial arrangement of proteins by twisting of
polypeptide chain= folding /helical coiling patterns in proteins (alpha-helix)
or zig-zag linear( beta-sheet) or mixed form by hydrogen bonding and
disulphide bonds .
•Secondary Structuresdenotesthestericrelationshipofaminoacidscloseto
eachother.
•One of the form of coiling of the polypeptide chain is right handed alpha-
helix.
•Since proteins are made up of L-amino acids , the coiling of polypeptide
chain into right handed alpha-helix is facilitated.
•Super secondaryStructures:indicate folding patterns in proteins
•Linus Pauling (Noble 1954)and Robert Corey (Noble 1951) proposed alpha-
helix and beta-pleated sheet structuresofpolypeptide chains.
•SecondaryStructures:spatial arrangement of proteins by twisting of
polypeptide chain= folding /helical coiling patterns in proteins (alpha-helix)
or zig-zag linear( beta-sheet) or mixed form by hydrogen bonding and
disulphide bonds .
•Secondary Structuresdenotesthestericrelationshipofaminoacidscloseto
eachother.
•One of the form of coiling of the polypeptide chain is right handed alpha-
helix.
•Since proteins are made up of L-amino acids , the coiling of polypeptide
chain into right handed alpha-helix is facilitated.
•Super secondaryStructures:indicate folding patterns in proteins
•Linus Pauling (Noble 1954)and Robert Corey (Noble 1951) proposed alpha-
helix and beta-pleated sheet structuresofpolypeptide chains.
Primary and Secondarystructure of Human Insulin
Carboxy-terminal end
A chain : Asparagine
B chain :Threonine
Amino-terminal end
A chain : Glycine
B chain : Phenylalanine
Apolypeptide chain :
21 amino acids
Bpolypeptide chain :
30 amino acids
intrachain disulphide bond :between
Cysteine residues( 6
th
amino acid of A
chain with11
th
amino acid of B chain)
interchain disulphide bonds
Carboxy-terminal end
A chain : Asparagine
B chain :Threonine
Amino-terminal end
A chain : Glycine
B chain : Phenylalanine
Apolypeptide chain :
21 amino acids
Bpolypeptide chain :
30 amino acids
intrachain disulphide bond :between
Cysteine residues( 6
th
amino acid of A
chain with11
th
amino acid of B chain)
interchain disulphide bonds
Different kinds of secondary structures
❖Different kinds of secondary structures:
1.Alpha-helix (helicoid state)
2.Beta-pleated sheet (stretched state)
3.Loop regions
4.Beta-bends or beta-turns
5.Disordered regions
6.Triple helix
❖Different kinds of secondary structures:
1.Alpha-helix (helicoid state)
2.Beta-pleated sheet (stretched state)
3.Loop regions
4.Beta-bends or beta-turns
5.Disordered regions
6.Triple helix
Alpha()-helix
•Alpha()-helix : is called Alpha() because the first structure elucidated by
Linus Pauling (Noble 1954)and Robert Corey (Noble 1951).It is most common
spatial structure of protein .
•If a backbone of polypeptide chain is twistedby equal amounts about each
-carbon, itforms a coilor helix. The -helix is a rod like structure .
•These hydrogen bonds have an essentially optimal nitrogen to oxygen (N-O)
distance of 2.8 A. Thus, carbonyl(CO)group of each amino acid is hydrogen
bonded to the -NH of the amino acid that is situated 4 residues ahead in a
linear sequence .
•The axial distance between adjacent amino acids is 1.5 Aand gives 3.6
amino acid residues per turn of helix.
•Alpha()-helix : is called Alpha() because the first structure elucidated by
Linus Pauling (Noble 1954)and Robert Corey (Noble 1951).It is most common
spatial structure of protein .
•If a backbone of polypeptide chain is twistedby equal amounts about each
-carbon, itforms a coilor helix. The -helix is a rod like structure .
•These hydrogen bonds have an essentially optimal nitrogen to oxygen (N-O)
distance of 2.8 A. Thus, carbonyl(CO)group of each amino acid is hydrogen
bonded to the -NH of the amino acid that is situated 4 residues ahead in a
linear sequence .
•The axial distance between adjacent amino acids is 1.5 Aand gives 3.6
amino acid residues per turn of helix.
Characteristicsof Alpha-helix (a type of Secondarystructure of proteins):1
❖Characteristicsof Alpha-helix:
1.The most common stable conformation formed spontaneously with the lowest energy.
2.right or left handed Spiral/helical /tightly coiled structure in the stable form. A right
handed helix turns in the direction that the fingers of right hand curl when its thumb
points in the direction the helix rises.
3.Stabilized by Hydrogen bonds (weak, strong enough due to large number to stabilize
alpha helix structure) of the main chain which forms the back bone. Side chains of amino
acids extend outwards from the central axis.
4.Hydrogen bonding occurs between the carboxyl oxygen of one peptide bond and the
amide nitrogen of another peptide bond and 3 amino acid residues apart / further down
in the chain (e.g. 5
th
is hydrogen bonded to 9
th
and 6
th
is bonded 10
th
and so on). All
peptide bonds except the first and the last in polypeptide chain participate in hydrogen
bonding.
5.Each peptide bond in the polypeptide chain participates in intrachain hydrogen bonding.
❖Characteristicsof Alpha-helix:
1.The most common stable conformation formed spontaneously with the lowest energy.
2.right or left handed Spiral/helical /tightly coiled structure in the stable form. A right
handed helix turns in the direction that the fingers of right hand curl when its thumb
points in the direction the helix rises.
3.Stabilized by Hydrogen bonds (weak, strong enough due to large number to stabilize
alpha helix structure) of the main chain which forms the back bone. Side chains of amino
acids extend outwards from the central axis.
4.Hydrogen bonding occurs between the carboxyl oxygen of one peptide bond and the
amide nitrogen of another peptide bond and 3 amino acid residues apart / further down
in the chain (e.g. 5
th
is hydrogen bonded to 9
th
and 6
th
is bonded 10
th
and so on). All
peptide bonds except the first and the last in polypeptide chain participate in hydrogen
bonding.
5.Each peptide bond in the polypeptide chain participates in intrachain hydrogen bonding.
Characteristicsof Alpha-helix (a type of Secondarystructure of proteins):2
6.Eachturnof Alpha-helix :
a.contains 3.6 amino acids residues /turn of the helix with the R group protruding outward
radially.
b.A rise along the central axis of 1.5Aper residue and travels distance of 5.4 nm/turn.
c.Spacing of each amino acid residue ( axial distance between amino acids) is 0.15nm (1.5
Atranslation).
6.The right handed -helix more stable and common than left handed helix. Left handed
helix are rare because of presence of L-amino acid found in protein which exclude left
handedness).
7.Proline , hydroxy proline and Glycine disrupt alpha-helix formation and introduce a kink
or a bend in the helix.
8.Large number of acidic (Asp,Glu) or basic amino acids (Lys , Arg,His)or amino acid with
bulky R group disrupt Alpha-helix.
9.Abundant in Myoglobin , Hemoglobin , Keratin of hair (-Keratin ), proteins in wooland
virtually, absent in Chymotrypsin.
6.Eachturnof Alpha-helix :
a.contains 3.6 amino acids residues /turn of the helix with the R group protruding outward
radially.
b.A rise along the central axis of 1.5Aper residue and travels distance of 5.4 nm/turn.
c.Spacing of each amino acid residue ( axial distance between amino acids) is 0.15nm (1.5
Atranslation).
6.The right handed -helix more stable and common than left handed helix. Left handed
helix are rare because of presence of L-amino acid found in protein which exclude left
handedness).
7.Proline , hydroxy proline and Glycine disrupt alpha-helix formation and introduce a kink
or a bend in the helix.
8.Large number of acidic (Asp,Glu) or basic amino acids (Lys , Arg,His)or amino acid with
bulky R group disrupt Alpha-helix.
9.Abundant in Myoglobin , Hemoglobin , Keratin of hair (-Keratin ), proteins in wooland
virtually, absent in Chymotrypsin.
Right and left-handed alpha-helix structure in protein molecule
•A Right-handed alpha-helix turns in
direction that fingers of right hand
curl when thumb points in direction
of helix rises.
•A left-handed alpha-helix turns in
direction that fingers of left hand curl
when thumb points in direction of
helix rises.
•A Right-handed alpha-helix turns in
direction that fingers of right hand
curl when thumb points in direction
of helix rises.
•A left-handed alpha-helix turns in
direction that fingers of left hand curl
when thumb points in direction of
helix rises.
Schematic diagram of alpha-helical structure of proteins
Alpha-helix :Each oxygen of C=O group of a peptide bond forms a hydrogen bond with the hydrogen atom
attached to the nitrogen in a peptide bond, four amino acids further along the polypeptide chain .
Each turn of Alpha-
helix travels
distance of 5.4
nm/turn.
Alpha-helix
Alpha-helix :Each oxygen of C=O group of a peptide bond forms a hydrogen bond with the hydrogen atom
attached to the nitrogen in a peptide bond, four amino acids further along the polypeptide chain .
Each turn of Alpha-
helix travels
distance of 5.4
nm/turn.
Alpha-helix
Alpha-helix (a type of Secondarystructure of proteins):3
Alpha-helix :Hydrogen bonding occurs between the carboxyl oxygen of one peptide bond and the amide
nitrogen of another peptide bond and 3 amino acid residues apart / further down in the chain(e.g. 5
th
is
hydrogen bonded to 9
th
and 6
th
is bonded 10
th
and so on). All peptide bonds except the first and the last in
polypeptide chain participate in hydrogen bonding.
Alpha-helix :Hydrogen bonding occurs between the carboxyl oxygen of one peptide bond and the amide
nitrogen of another peptide bond and 3 amino acid residues apart / further down in the chain(e.g. 5
th
is
hydrogen bonded to 9
th
and 6
th
is bonded 10
th
and so on). All peptide bonds except the first and the last in
polypeptide chain participate in hydrogen bonding.
Schematic diagram of alpha-helical structure of proteins
Alpha-helix :Stabilized by Hydrogen bonds (weak, strong enough due to large number to stabilize alpha-helix
structure) of the main chain which forms the back bone. Side chains of amino acids extend outwards from
the central axis.
Side chains of amino acids extend
outwards from the central axis.
Stabilized by Hydrogen
bonds
Alpha-helix :Stabilized by Hydrogen bonds (weak, strong enough due to large number to stabilize alpha-helix
structure) of the main chain which forms the back bone. Side chains of amino acids extend outwards from
the central axis.
Side chains of amino acids extend
outwards from the central axis.
Stabilized by Hydrogen
bonds
Examples of proteins with alpha-helical structure
❖Alpha-helical structure occur in both fibrous and globular proteins.
Fibrous proteins with alpha-helical
structure
Globular proteins with alpha-helical
structure
-Keratin of hair , nail , skin Hemoglobin(80%)
Fibrinofblood Myoglobin
Myosin and Tropomyosin of muscle
Proteins in wool
Digestive enzyme→Chymotrypsin is virtually devoid of alpha-helix in its
structure.
❖Alpha-helical structure occur in both fibrous and globular proteins.
Fibrous proteins with alpha-helical
structure
Globular proteins with alpha-helical
structure
-Keratin of hair , nail , skin Hemoglobin(80%)
Fibrinofblood Myoglobin
Myosin and Tropomyosin of muscle
Proteins in wool
Digestive enzyme→Chymotrypsin is virtually devoid of alpha-helix in its
structure.
Formation of hydrogen bond in alpha()-helix
NH
3
+
–CH–CO–NH–CH–CO–NH–CH–CO–NH–CH–CO–NH-CH–COO
-
I I I I I
R
1
R
2
R
3
R
4
R
5
---------Hydrogen bond ( N-O distance =2.8 A)-------------
3.6 amino acid residues
NH
3
+
–CH–CO–NH–CH–CO–NH–CH–CO–NH–CH–CO–NH-CH–COO
-
I I I I I
R
1
R
2
R
3
R
4
R
5
---------Hydrogen bond ( N-O distance =2.8 A)-------------
3.6 amino acid residues
Helix destabilizing amino acids
❖Helix destabilizing (helix beakers)amino acids : Glycine , Proline
❖Prolineasa helix beaker: since nitrogen of Proline residue in a peptide
linkage has no substituted hydrogen (as it has imino NH-group instead of
amino group) for the formation of hydrogen bond with other residue , Proline
fits only the first turn of an alpha-helix. Elsewhere, it produces bend and turn.
❖Glycineasa helix beaker: all bends in alpha-helix are not caused by Proline
residue but bend often occurs also at Glycine residues as side chain of Glycine
is small.
❖Helix destabilizing (helix beakers)amino acids : Glycine , Proline
❖Prolineasa helix beaker: since nitrogen of Proline residue in a peptide
linkage has no substituted hydrogen (as it has imino NH-group instead of
amino group) for the formation of hydrogen bond with other residue , Proline
fits only the first turn of an alpha-helix. Elsewhere, it produces bend and turn.
❖Glycineasa helix beaker: all bends in alpha-helix are not caused by Proline
residue but bend often occurs also at Glycine residues as side chain of Glycine
is small.
Peptide bond formation with Proline
Schematic diagram
H H
NH
2
–C–CO NC–COOH →NH
2–CH–CO– C–COOH +
I I
R
1
R
1
Aminoacid Prolinepeptide nitrogen of Prolinehas no substituted hydrogen
Schematic diagram
H H
NH
2
–C–CO NC–COOH →NH
2–CH–CO– C–COOH +
I I
R
1
R
1
Aminoacid Prolinepeptide nitrogen of Prolinehas no substituted hydrogen
Structural importance of Alpha-helix
❖Structural importance of alpha-helix : Several alpha-helices can coil
around one another like a twisted twined cable forming strongstiff
bundlesof fibers and give mechanicalsupport.
❖Structural importance of alpha-helix : Several alpha-helices can coil
around one another like a twisted twined cable forming strongstiff
bundlesof fibers and give mechanicalsupport.
Characteristicsof Beta-pleatedsheet(Secondarystructure of proteins)
❖Characteristicsof Beta-pleatedsheet:where proposed/described by Linus Pauling (Noble
1954)and Robert Corey (Noble 1951). It is Beta because , it was the second type of structure
after alpha-helixthey elucidated.
1.When alpha-helix of keratin is stretched the hydrogen bonds are broken and new
hydrogen bonds are formed between -CO and NH-of adjacent parallel chain / neighboring
polypeptide segments giving rise to an arrangement of the backbone of protein
molecule→Beta-pleatedsheet. (Beta-sheet appear pleated).
2.is stabilized by the hydrogen bonds .
3.Hydrogen bonding occurs between two polypeptide chains(H-bonds are intrachain) or
two regions (neighboring segments) of a single chain of polypeptide chain (H-bonds are
interchain).
4.Composed of 2 or more segments of fully extended polypeptide chains.
5.Two polypeptide chains in a beta-pleated sheet may run in the samedirection(parallel
beta-pleated sheets ) with regard to amino and carboxy terminal ends of polypeptide
chain or in the oppositedirections(anti-parallel beta-pleated sheets).
6.Distance between adjacent amino acid residue is 3.5 A(translation).
7.Major structural motif in fibroin of silk (anti-parallel), flavodoxin(parallel), Carbonic
anhydrase(both),some regions of globular proteins like chymotrypsin, ribonuclease.
❖Characteristicsof Beta-pleatedsheet:where proposed/described by Linus Pauling (Noble
1954)and Robert Corey (Noble 1951). It is Beta because , it was the second type of structure
after alpha-helixthey elucidated.
1.When alpha-helix of keratin is stretched the hydrogen bonds are broken and new
hydrogen bonds are formed between -CO and NH-of adjacent parallel chain / neighboring
polypeptide segments giving rise to an arrangement of the backbone of protein
molecule→Beta-pleatedsheet. (Beta-sheet appear pleated).
2.is stabilized by the hydrogen bonds .
3.Hydrogen bonding occurs between two polypeptide chains(H-bonds are intrachain) or
two regions (neighboring segments) of a single chain of polypeptide chain (H-bonds are
interchain).
4.Composed of 2 or more segments of fully extended polypeptide chains.
5.Two polypeptide chains in a beta-pleated sheet may run in the samedirection(parallel
beta-pleated sheets ) with regard to amino and carboxy terminal ends of polypeptide
chain or in the oppositedirections(anti-parallel beta-pleated sheets).
6.Distance between adjacent amino acid residue is 3.5 A(translation).
7.Major structural motif in fibroin of silk (anti-parallel), flavodoxin(parallel), Carbonic
anhydrase(both),some regions of globular proteins like chymotrypsin, ribonuclease.
Intrachain hydrogen bonds (within single polypeptide chain) and interchain
hydrogen bonds (between two or more polypeptide chains )
Interchain hydrogen bonds : are formed between amide hydrogen ( NH) of one polypeptide chain
and carbonyl (C=O) of neighboring polypeptide chain.
Intrachain hydrogen bonds : are formed between amide hydrogen ( NH) of one polypeptide chain
and carbonyl (C=O) of the same polypeptide chain.
hydrogen bonds (between two or more polypeptide chains )
Interchain hydrogen bonds : are formed between amide hydrogen ( NH) of one polypeptide chain
and carbonyl (C=O) of neighboring polypeptide chain.
Intrachain hydrogen bonds : are formed between amide hydrogen ( NH) of one polypeptide chain
and carbonyl (C=O) of the same polypeptide chain.
Comparison of Alpha-helix and Beta-pleated sheet: secondary
structure ofproteins
Criteria Alpha-helixBeta-pleated sheet
Structure Coiled rod like Fully extended sheet like
Axial distance between amino acids 1.5A 3.5A
Number of constituent polypeptide chainOne One or more polypeptide
chains
Stabilized by hydrogen bonds between
NH and C= O groups in
the same
polypeptide chain
Different /the same
polypeptide chain
hydrogen bonds are Parallel to
polypeptide
backbone
Perpendicular to
polypeptide backbone
structure ofproteins
Criteria Alpha-helixBeta-pleated sheet
Structure Coiled rod like Fully extended sheet like
Axial distance between amino acids 1.5A 3.5A
Number of constituent polypeptide chainOne One or more polypeptide
chains
Stabilized by hydrogen bonds between
NH and C= O groups in
the same
polypeptide chain
Different /the same
polypeptide chain
hydrogen bonds are Parallel to
polypeptide
backbone
Perpendicular to
polypeptide backbone
Comparison of Alpha-helix and Beta-pleated sheet: secondarystructures ofproteins
hydrogen bonds are Perpendicularto
polypeptide backbone.
hydrogen bonds are Parallel
to polypeptide backbone
Coiled rod like Fully extended sheet like
Axial distance between
amino acids 1. 5 A
Axial distance between amino acids 3. 5 A
One constituent polypeptide
chain
Alpha-helix Beta-pleatedsheet
One or more constituent polypeptide chain
hydrogen bonds are Perpendicularto
polypeptide backbone.
hydrogen bonds are Parallel
to polypeptide backbone
Coiled rod like Fully extended sheet like
Axial distance between
amino acids 1. 5 A
Axial distance between amino acids 3. 5 A
One constituent polypeptide
chain
Alpha-helix Beta-pleatedsheet
One or more constituent polypeptide chain
Alpha-helix ,Beta-pleated sheet :secondarystructures ofimportantproteins
Alpha-helix: abundant in Myoglobin , hemoglobin , Keratin of hair (-Keratin), proteins in wool and absent
in chymotrypsin
Beta-pleatedsheet : fibroin of silk ,some regions of globular proteins like chymotrypsin, ribonuclease
Alpha-helix: abundant in Myoglobin , hemoglobin , Keratin of hair (-Keratin), proteins in wool and absent
in chymotrypsin
Beta-pleatedsheet : fibroin of silk ,some regions of globular proteins like chymotrypsin, ribonuclease
The arrangement of polypeptide chains in beta-pleated sheet conformation
❖The arrangement of polypeptide chains in beta-pleated sheet conformation
can occur two ways:
1.Parallel beta-pleated sheet
2.Anti-parallel beta-pleated sheet
➢A beta-sheet can also be formed by either a single polypeptide chain folding
back on to itself (H-bonds are intrachain and stabilized by intramolecular
hydrogen bonding ) or separate polypeptide chains (H-bonds are interchain) .
➢As such , the -helix and -sheet are commonly found in the same protein
structure . In the globular proteins , -sheet form the core structure.
❖The arrangement of polypeptide chains in beta-pleated sheet conformation
can occur two ways:
1.Parallel beta-pleated sheet
2.Anti-parallel beta-pleated sheet
➢A beta-sheet can also be formed by either a single polypeptide chain folding
back on to itself (H-bonds are intrachain and stabilized by intramolecular
hydrogen bonding ) or separate polypeptide chains (H-bonds are interchain) .
➢As such , the -helix and -sheet are commonly found in the same protein
structure . In the globular proteins , -sheet form the core structure.
Intrachain hydrogen bonds (within single polypeptide chain) and interchain
hydrogen bonds (between two or more polypeptide chains )
Interchain hydrogen bonds : are formed between amide hydrogen ( NH) of one polypeptide chain
and carbonyl (C=O) of neighboring polypeptide chain
Intrachain hydrogen bonds : are formed between amide hydrogen ( NH) of one polypeptide chain
and carbonyl (C=O) of the same polypeptide chain
hydrogen bonds (between two or more polypeptide chains )
Interchain hydrogen bonds : are formed between amide hydrogen ( NH) of one polypeptide chain
and carbonyl (C=O) of neighboring polypeptide chain
Intrachain hydrogen bonds : are formed between amide hydrogen ( NH) of one polypeptide chain
and carbonyl (C=O) of the same polypeptide chain
Hydrogen bonds in beta-pleated sheet structure
H O H
N C N
C N C
O H O
C N C
O
I II I
II II
II
II
I
I
•
•
•
•
H O
•
•N
H
I
N
I
H
•
C
Hydrogen bond between chains
Beta-pleated sheets(or simply sheets )are composed of two or more segments of fully
extended peptide chains.
Schematic diagram
H O H
N C N
C N C
O H O
C N C
O
I II I
II II
II
II
I
I
•
•
•
•
H O
•
•N
H
I
N
I
H
•
C
Hydrogen bond between chains
Beta-pleated sheets(or simply sheets )are composed of two or more segments of fully
extended peptide chains.
Schematic diagram
Parallel and anti-parallel beta-pleated sheet
Parallel beta-pleated
sheet :same direction of N
& C-terminal ends of
peptide/Two polypeptide
chains run in the same
directions (parallel).
Anti-parallelbeta-pleated
sheet: Opposite direction
of N & C-terminal ends
peptide/Two polypeptide
chains run in the opposite
directions (antiparallel).
Parallel beta-pleated
sheet :same direction of N
& C-terminal ends of
peptide/Two polypeptide
chains run in the same
directions (parallel).
Anti-parallelbeta-pleated
sheet: Opposite direction
of N & C-terminal ends
peptide/Two polypeptide
chains run in the opposite
directions (antiparallel).
Structure of beta-pleated sheet
N-terminal C–terminal
N-terminal C-terminal
C-terminal N-terminal
The polypeptide chains in the beta()–sheets may be arranged either in parallel
(the same direction) or anti-parallel (opposite direction).
Parallel beta-pleated sheets
Antiparallel beta-pleated sheets
N-terminal C–terminal
N-terminal C-terminal
C-terminal N-terminal
The polypeptide chains in the beta()–sheets may be arranged either in parallel
(the same direction) or anti-parallel (opposite direction).
Parallel beta-pleated sheets
Antiparallel beta-pleated sheets
Properties of Beta-pleatedsheet(Secondarystructure of proteins)
Parallel beta-pleatedsheet: the polypeptide are side by side and lie in same direction of N
& C-terminal ends of peptide, so that their terminal residues are at the same end ( N-terminal
faces to N-terminal ).It is stabilized by intrachain hydrogen bonds.
Anti-parallel beta-pleatedsheet : Opposite direction of N & C-terminal ends peptide.
Parallel beta-pleatedsheet: the polypeptide are side by side and lie in same direction of N
& C-terminal ends of peptide, so that their terminal residues are at the same end ( N-terminal
faces to N-terminal ).It is stabilized by intrachain hydrogen bonds.
Anti-parallel beta-pleatedsheet : Opposite direction of N & C-terminal ends peptide.
Anti-parallelbeta-pleated
sheet: the polypeptide lie in
opposite directions i.e. N –
terminal end of one
polypeptide is next to C –
terminal of the other. (N-
terminal faces C-terminal
end of peptide-Anti-parallel
directions ).
It is stabilized by interchain
hydrogen bonds.
Anti parallel pleatedbeta-sheet ofSecondarystructure ofproteins
sheet: the polypeptide lie in
opposite directions i.e. N –
terminal end of one
polypeptide is next to C –
terminal of the other. (N-
terminal faces C-terminal
end of peptide-Anti-parallel
directions ).
It is stabilized by interchain
hydrogen bonds.
Anti parallel pleatedbeta-sheet ofSecondarystructure ofproteins
Clinical application of beta-pleated sheet :Secondarystructure ofproteins
❖Clinical application of beta-pleated sheet :Secondarystructure ofproteins
found in both fibrous and globular proteins.
•Anti-parallel beta-sheets conformation is less common in human proteins.
❖Occurrenceofbeta-sheet :
1.Silkfibroin(the best example in nature)
2.Amyloidin human tissue: a protein that accumulates in Amyloidosisand
Alzheimer’sdisease.Dementiaoccurring in middle age associated with this
Amyloidosis .
❖Clinical application of beta-pleated sheet :Secondarystructure ofproteins
found in both fibrous and globular proteins.
•Anti-parallel beta-sheets conformation is less common in human proteins.
❖Occurrenceofbeta-sheet :
1.Silkfibroin(the best example in nature)
2.Amyloidin human tissue: a protein that accumulates in Amyloidosisand
Alzheimer’sdisease.Dementiaoccurring in middle age associated with this
Amyloidosis .
Loopregionsand their Importance
❖Loopregions:
•About half of the residues in a typical globular protein are present in alpha-
helices or beta-sheet . Remaining residues are present in loop or coil
conformation. Loop regions though irregularly ordered (lacking regular
secondary structure) are biologically important as they are more ordered
secondary structure.
•Loop or coiled the random coils (disordered and biological unimportant
conformation of denatured proteins).
❖Importanceofloopregions: form the antigen-binding sites of antibodies.
❖Loopregions:
•About half of the residues in a typical globular protein are present in alpha-
helices or beta-sheet . Remaining residues are present in loop or coil
conformation. Loop regions though irregularly ordered (lacking regular
secondary structure) are biologically important as they are more ordered
secondary structure.
•Loop or coiled the random coils (disordered and biological unimportant
conformation of denatured proteins).
❖Importanceofloopregions: form the antigen-binding sites of antibodies.
Beta-bend or beta-turn and its Importance
❖Beta-bend or beta-turn or hairpin turn or reverse turn : refers to the segment , in
which a polypeptide chain abruptly reverses direction and often connects the ends
of the adjacent antiparallel beta-strands hence they are named as beta-turn.
Globular proteins containBeta-bends.
❖Characteristicsof beta-bend(-bend) :
1.consists of four successive amino acid residues.
2.Frequently contains Proline or Glycine or both.
3.is stabilized by Intrachain disulphide bridges and hydrogen bonds (hydrogen bond
is formed between the first amino acid to the forth in the bend).
4.occur primarily at protein surfaces and impart globular shape (rather than
linearity) to proteins.
5.Promote the formation of anti-parallel beta –pleated sheets .
6.Importanceof beta-bends: they help in the formation of compact globular
structure.
❖Beta-bend or beta-turn or hairpin turn or reverse turn : refers to the segment , in
which a polypeptide chain abruptly reverses direction and often connects the ends
of the adjacent antiparallel beta-strands hence they are named as beta-turn.
Globular proteins containBeta-bends.
❖Characteristicsof beta-bend(-bend) :
1.consists of four successive amino acid residues.
2.Frequently contains Proline or Glycine or both.
3.is stabilized by Intrachain disulphide bridges and hydrogen bonds (hydrogen bond
is formed between the first amino acid to the forth in the bend).
4.occur primarily at protein surfaces and impart globular shape (rather than
linearity) to proteins.
5.Promote the formation of anti-parallel beta –pleated sheets .
6.Importanceof beta-bends: they help in the formation of compact globular
structure.
Beta bends & non –repetitive secondarystructure of proteins
Beta-bends may be formed in many proteins by the abrupt U-turn folding of the chain.
Intrachain disulphide bridges and hydrogen bonds stabilize these bends .
Beta-bends may be formed in many proteins by the abrupt U-turn folding of the chain.
Intrachain disulphide bridges and hydrogen bonds stabilize these bends .
Disorderedregion and its Importance
•Not all residues are necessarily present or ordered secondary
structure.
•Specific residues of many proteins exist in numerous conformation in
solution and thus they are called Disorderedregions.
•ManyDisorderedregion become orderedregion when a specific
ligand is bound .
•e.g. ThestabilizationofDisorderedregions of the catalytic sites of
many enzymes when ligand is bound .
•Importanceof Disorderedregion : gives flexibility and performs a
vital biological role.
•Not all residues are necessarily present or ordered secondary
structure.
•Specific residues of many proteins exist in numerous conformation in
solution and thus they are called Disorderedregions.
•ManyDisorderedregion become orderedregion when a specific
ligand is bound .
•e.g. ThestabilizationofDisorderedregions of the catalytic sites of
many enzymes when ligand is bound .
•Importanceof Disorderedregion : gives flexibility and performs a
vital biological role.
Disorderedregion of enzyme and its Importance
Schematic diagram
ManyDisorderedregion become orderedregion when a specific ligand is bound .
Disorderedregion gives flexibility and performs a vital biological role.
Disorderedregions of
enzyme-catalytic site
orderedregions of
enzyme
Substrate added to
enzyme catalyzed
reaction mixture
Enzyme with
Disorderedregions
set free at the end of
reaction
Product
Enzyme-substrate complex –induced fit
+
Schematic diagram
ManyDisorderedregion become orderedregion when a specific ligand is bound .
Disorderedregion gives flexibility and performs a vital biological role.
Disorderedregions of
enzyme-catalytic site
orderedregions of
enzyme
Substrate added to
enzyme catalyzed
reaction mixture
Enzyme with
Disorderedregions
set free at the end of
reaction
Product
Enzyme-substrate complex –induced fit
+
Super secondary structures of proteins
❖A protein molecule may contain all types of arrangements in different parts .
Thus , a part may form an -helix to be followed by -pleated sheets which
may include parallel or anti-parallel regions with intervening turns,loop
regions and disordered regions. Such combinations of secondary structural
features are called Super secondary structures.
➢These grouping of certain secondary structural elements of proteins occur
in many unrelated globular proteins.
❖A protein molecule may contain all types of arrangements in different parts .
Thus , a part may form an -helix to be followed by -pleated sheets which
may include parallel or anti-parallel regions with intervening turns,loop
regions and disordered regions. Such combinations of secondary structural
features are called Super secondary structures.
➢These grouping of certain secondary structural elements of proteins occur
in many unrelated globular proteins.
Characteristic properties of Super secondary structures of proteins
❖Characteristic properties of Super secondary structures of proteins:
1.Folding patterns involving -helices, -pleated sheets (which may be parallel or
anti-parallel regions with intervening turns),loop regions and disordered
regions.
2.--
2: in this structure ,an -helix connects two parallel strands of -pleated
sheets. It is the most common motif.
3.-hairpin: consists of antiparallel -sheets joined by relatively tight reverse
turn/ short loops.
4.motif:two successive anti-parallel helices packed against each other with
their axis inclined.
5.-barrel: extended -pleated sheets role up to form three different types of
barrels
6.Globular proteins like Chymotrypsin , Myoglobin and Ribonuclease have Super
secondary structures instead of uniform secondary structures.
7.The secondary and Super secondary structures of large proteins are recognized
as domainsor motifs.
❖Characteristic properties of Super secondary structures of proteins:
1.Folding patterns involving -helices, -pleated sheets (which may be parallel or
anti-parallel regions with intervening turns),loop regions and disordered
regions.
2.--
2: in this structure ,an -helix connects two parallel strands of -pleated
sheets. It is the most common motif.
3.-hairpin: consists of antiparallel -sheets joined by relatively tight reverse
turn/ short loops.
4.motif:two successive anti-parallel helices packed against each other with
their axis inclined.
5.-barrel: extended -pleated sheets role up to form three different types of
barrels
6.Globular proteins like Chymotrypsin , Myoglobin and Ribonuclease have Super
secondary structures instead of uniform secondary structures.
7.The secondary and Super secondary structures of large proteins are recognized
as domainsor motifs.
Domains of the globularproteins
❖Domainsof the globularprotein:
➢The term domainis used to represent the basic structural and functional units of
protein with tertiary structure(denotes a compact globular functional unit of
protein).
➢Relatively independent region and may represent a functional unit.
➢are usually connected with relatively flexible areas of protein (e.g. immunoglobulin)
❖3 Domains of Phenylalanine hydroxylase :
a.Catalytic
b.Regulatory
c.Protein-protein interaction domain
❖Calmodulin: a calcium binding regulatory protein(regulates intracellular calcium
levels )
❖A polypeptide with 200 amino acids normally consists of two or more domains.
❖Domainsof the globularprotein:
➢The term domainis used to represent the basic structural and functional units of
protein with tertiary structure(denotes a compact globular functional unit of
protein).
➢Relatively independent region and may represent a functional unit.
➢are usually connected with relatively flexible areas of protein (e.g. immunoglobulin)
❖3 Domains of Phenylalanine hydroxylase :
a.Catalytic
b.Regulatory
c.Protein-protein interaction domain
❖Calmodulin: a calcium binding regulatory protein(regulates intracellular calcium
levels )
❖A polypeptide with 200 amino acids normally consists of two or more domains.
--
2 Protein motifs
--
2: an -helix connects two
parallel strands of -pleated sheets.
Folding patterns involving -
helices and -pleated sheets.
2 Protein motifs
--
2: an -helix connects two
parallel strands of -pleated sheets.
Folding patterns involving -
helices and -pleated sheets.
motif and -hairpin Protein motifs(Super secondary structure of proteins)
motif: two successive anti-parallel
helices packed against each other with their
axis inclined.
-hairpin : consists of antiparallel -sheets joined
by relatively tight reverse turn/ short loops.
motif: two successive anti-parallel
helices packed against each other with their
axis inclined.
-hairpin : consists of antiparallel -sheets joined
by relatively tight reverse turn/ short loops.
-barrel Protein motifs(Super secondary structure of proteins)
-barrel: extended -pleated sheets role
up to form different types of barrels
Role of Super secondary structure of
membrane proteins
-barrel: extended -pleated sheets role
up to form different types of barrels
Role of Super secondary structure of
membrane proteins
-barrels located across Mitochondrial outer membrane
-barrelslocated across the Mitochondrial outer membrane facilitate transport of moieties
associated with functions of mitochondrion (e.g. Biological oxidation , Urea cycle etc. ).
-barrelslocated across the Mitochondrial outer membrane facilitate transport of moieties
associated with functions of mitochondrion (e.g. Biological oxidation , Urea cycle etc. ).
Protein motifs(Super secondary structure of proteins)
Predominant Specific structural motifs of common proteins
Protein Predominant Specific structural motifs present
Myoglobin Alpha-helix and beta-pleated sheets
Flavodoxin Parallel beta-pleated sheets
Super oxide dismutase Anti-parallel beta-pleated sheets
Fibroin of silk anti-parallel beta-pleated sheets
Carbonic anhydraseBoth Parallel and Anti-parallel beta-pleated
sheets
Keratin Alpha-helix →Coiled coil
Collagen Triple-helix
Elastin No specific motif
Protein Predominant Specific structural motifs present
Myoglobin Alpha-helix and beta-pleated sheets
Flavodoxin Parallel beta-pleated sheets
Super oxide dismutase Anti-parallel beta-pleated sheets
Fibroin of silk anti-parallel beta-pleated sheets
Carbonic anhydraseBoth Parallel and Anti-parallel beta-pleated
sheets
Keratin Alpha-helix →Coiled coil
Collagen Triple-helix
Elastin No specific motif
Approximate amount of a alpha -helix and beta-structure in some single chain protein
Protein Totalresidue Alpha-helix
( residue %)
Beta-structure
( residue %)
Myoglobin 153 78 0
Cytochrome C 104 39 0
Lysozyme 129 40 12
Ribonuclease 124 26 35
Chymotrypsin 247 14 45
Carboxy peptidase 307 38 17
Data from C. R. Cantor and P.R. Schimnel,Biophysical chemistry , the conformation of biological macromolecules p 100 1980
Protein Totalresidue Alpha-helix
( residue %)
Beta-structure
( residue %)
Myoglobin 153 78 0
Cytochrome C 104 39 0
Lysozyme 129 40 12
Ribonuclease 124 26 35
Chymotrypsin 247 14 45
Carboxy peptidase 307 38 17
Data from C. R. Cantor and P.R. Schimnel,Biophysical chemistry , the conformation of biological macromolecules p 100 1980
TertiaryStructure of proteins
Tertiary Structure :
Three dimensional structure
generated by interaction between
the amino acid residues of functional
proteins.
Tertiary Structure :
Three dimensional structure
generated by interaction between
the amino acid residues of functional
proteins.
TertiaryStructure of proteins
❖Tertiary structure of globular proteinsdefines the steric relationship of amino
acids which are far apart from each other in the linear sequence but are close in
three dimensional aspects i.e. Three-dimensional structure of globular proteins is
dependent on the primary structure.
•It is a compact structure with hydrophobic side chains held interior while
hydrophilic groups are on the surface of the protein molecule. This arrangement
ensures stability of the molecules.
•Three-dimensional structuralconformationofglobularproteins provides and
maintains the functional characteristics.
•Functions of globularproteins are maintained because of their ability to recognize
and interact with a variety of molecules .
•This structure reflects the overall shape of the molecule.
•Primarystructure of protein is folded to form compact, biologically stable and active
conformationi.e. a three-dimensionalglobularprotein.It is referred as its Tertiary
structure.
•e.g. Insulin ,Myoglobin
❖Tertiary structure of globular proteinsdefines the steric relationship of amino
acids which are far apart from each other in the linear sequence but are close in
three dimensional aspects i.e. Three-dimensional structure of globular proteins is
dependent on the primary structure.
•It is a compact structure with hydrophobic side chains held interior while
hydrophilic groups are on the surface of the protein molecule. This arrangement
ensures stability of the molecules.
•Three-dimensional structuralconformationofglobularproteins provides and
maintains the functional characteristics.
•Functions of globularproteins are maintained because of their ability to recognize
and interact with a variety of molecules .
•This structure reflects the overall shape of the molecule.
•Primarystructure of protein is folded to form compact, biologically stable and active
conformationi.e. a three-dimensionalglobularprotein.It is referred as its Tertiary
structure.
•e.g. Insulin ,Myoglobin
Tertiary structure of Human Insulin
In 1953 , FrederickSangerdetermined primary structure of Insulin (a pancreatic protein hormone) and
showed for the first time that a protein has a preciselydefinedaminoacidsequence(primarystructure).
Primarystructure of Human Insulin is folded to form compact, biologically stable and active conformation
i.e. a three-dimensionalglobularprotein.It is referred as its Tertiary structure.
In 1953 , FrederickSangerdetermined primary structure of Insulin (a pancreatic protein hormone) and
showed for the first time that a protein has a preciselydefinedaminoacidsequence(primarystructure).
Primarystructure of Human Insulin is folded to form compact, biologically stable and active conformation
i.e. a three-dimensionalglobularprotein.It is referred as its Tertiary structure.
TertiaryStructure of Myoglobin(Mb)
Myoglobin : Primary structure similar to single monomeric unit of Hemoglobin with a single polypeptide chain having
153 amino acids ( molecular weight 16700) . It haseight alpha –helices (A to H) and one heme group( iron containing
porphyrin) to facilitate its function of oxygen storage in cardiac and skeletal muscles in human body, Whales and Seals .
Myoglobin : Primary structure similar to single monomeric unit of Hemoglobin with a single polypeptide chain having
153 amino acids ( molecular weight 16700) . It haseight alpha –helices (A to H) and one heme group( iron containing
porphyrin) to facilitate its function of oxygen storage in cardiac and skeletal muscles in human body, Whales and Seals .
TertiaryStructure of Hemoglobin (Hb)
Hemoglobin : Tetrameric with 4 heme groups. Each polypeptide chain has similar structure to single
polypeptide chain of Myoglobin .It has a lower affinity for oxygen than Myoglobin. Four subunits of Hb
function cooperatively .Tetrameric structure of hemoglobin facilitates saturation with O
2 inthelungand
release of oxygen as it travels through the capillary bed.
Hemoglobin : Tetrameric with 4 heme groups. Each polypeptide chain has similar structure to single
polypeptide chain of Myoglobin .It has a lower affinity for oxygen than Myoglobin. Four subunits of Hb
function cooperatively .Tetrameric structure of hemoglobin facilitates saturation with O
2 inthelungand
release of oxygen as it travels through the capillary bed.
Covalentbonds stabilizingprotein structure
❖Proteins are stabilized by three types of covalentbonds:
1.Peptidebonds
2.Disulphidebonds
3.Lysinonorleucine bonds
❖Proteins are stabilized by three types of covalentbonds:
1.Peptidebonds
2.Disulphidebonds
3.Lysinonorleucine bonds
Peptide bonds : Covalentbonds stabilizingprotein structure
•Formation of peptide bond = a
covalent bond is formed by amide
linkage between the -carboxyl
group of one amino acid and -
amino group of another amino acid
by removal of a water molecule.
•Successive amino acids are
joined/cemented by peptide bonds
( -CO-NH) in proteins .
➢The peptide bonds form strong
backbone of polypeptide and side
chains of amino acid residue project
outside the peptide backbone.
Dipeptide :two amino acids and one peptide bond ( not two bonds)
•Formation of peptide bond = a
covalent bond is formed by amide
linkage between the -carboxyl
group of one amino acid and -
amino group of another amino acid
by removal of a water molecule.
•Successive amino acids are
joined/cemented by peptide bonds
( -CO-NH) in proteins .
➢The peptide bonds form strong
backbone of polypeptide and side
chains of amino acid residue project
outside the peptide backbone.
Dipeptide :two amino acids and one peptide bond ( not two bonds)
Lysinonorleucine bonds: Covalent bonds responsible for protein structure
❖Lysinonorleucine bonds:
•Abondformedbetweenoxidizedlysine residue with unmodified lysine side
chain to form a crosslink, both within and between the triple helix units.
e.g. Collagen
•Cross links confer tensile strength to the protein .
❖Lysinonorleucine bonds:
•Abondformedbetweenoxidizedlysine residue with unmodified lysine side
chain to form a crosslink, both within and between the triple helix units.
e.g. Collagen
•Cross links confer tensile strength to the protein .
Structure of collagen Type 1
❖Structure of collagen Type 1:
1.Triple-strandedhelicalstructurepresentthroughoutthe collagen
molecule
2.Shape: rod-likemolecule →1.4 nm diameter and 300 nm length
3.Number of Amino acid residues : 1000 per for each polypeptide
chain (3000 /molecule)
4.Amino acid contribution :1/3 rdof amino acids are Glycine (every
third amino acid in collagen is Glycine.
5.Repetitive amino acid sequence : (Gly–X –Y )n,where X and Y
represent other amino acids
6.Proline and hydroxyproline :100 per for each polypeptide chain
7.Function of Proline and hydroxyproline : confer rigidity to the
collagen molecule
8.Collagen Fibril formation :Triple helical molecule of collagen
assemble to form elongated fibrils . It occurs by a quarter staggered
alignment i.e. each triple helix is displaced longitudinally from its
neighbor collagen molecule by about one-quarter of its length
9.Collagen Fiber formation :Collagen Fibrils assemble to form rod like
fibers .
10.Strength of Collagen Fiber :contributed by covalent crosslinkingof
formed between Lysine and hydroxylysine and also between Proline
and hydroxyproline.
❖Structure of collagen Type 1:
1.Triple-strandedhelicalstructurepresentthroughoutthe collagen
molecule
2.Shape: rod-likemolecule →1.4 nm diameter and 300 nm length
3.Number of Amino acid residues : 1000 per for each polypeptide
chain (3000 /molecule)
4.Amino acid contribution :1/3 rdof amino acids are Glycine (every
third amino acid in collagen is Glycine.
5.Repetitive amino acid sequence : (Gly–X –Y )n,where X and Y
represent other amino acids
6.Proline and hydroxyproline :100 per for each polypeptide chain
7.Function of Proline and hydroxyproline : confer rigidity to the
collagen molecule
8.Collagen Fibril formation :Triple helical molecule of collagen
assemble to form elongated fibrils . It occurs by a quarter staggered
alignment i.e. each triple helix is displaced longitudinally from its
neighbor collagen molecule by about one-quarter of its length
9.Collagen Fiber formation :Collagen Fibrils assemble to form rod like
fibers .
10.Strength of Collagen Fiber :contributed by covalent crosslinkingof
formed between Lysine and hydroxylysine and also between Proline
and hydroxyproline.
Disulfidebonds:Covalentbonds stabilizingprotein structure
❖Proteins are stabilized by three types of covalentbonds(peptidebonds,
disulphidebonds and Lysinonorleucine bonds).
•Cysteine: with functional group -SH (sulfhydryl)
•Cystine: functional group -S-S-(disulphide)
•A covalent disulfide (-S-S)bond formed between the sulfhydryl group (-SH)of two
Cysteine residues in the same or different polypeptide chains.
•Intra chain S-S bond→Cysteine at 6
th
position linked to that at 11
th
position of A
chain of Insulin
❖Inter chain S-S bonds :
(1)Cysteine at 20
th
position of Achain is linked to that at 19
th
position of Bchain of
Insulin
(2) Cysteine at 7
th
position of Achain is linked to that at 7
th
position of Bchain of
Insulin
➢These disulfidebonds contribute to structural conformation and stability of
proteins . Performic acid cleaves the disulfidebonds between polypeptide units.
❖Proteins are stabilized by three types of covalentbonds(peptidebonds,
disulphidebonds and Lysinonorleucine bonds).
•Cysteine: with functional group -SH (sulfhydryl)
•Cystine: functional group -S-S-(disulphide)
•A covalent disulfide (-S-S)bond formed between the sulfhydryl group (-SH)of two
Cysteine residues in the same or different polypeptide chains.
•Intra chain S-S bond→Cysteine at 6
th
position linked to that at 11
th
position of A
chain of Insulin
❖Inter chain S-S bonds :
(1)Cysteine at 20
th
position of Achain is linked to that at 19
th
position of Bchain of
Insulin
(2) Cysteine at 7
th
position of Achain is linked to that at 7
th
position of Bchain of
Insulin
➢These disulfidebonds contribute to structural conformation and stability of
proteins . Performic acid cleaves the disulfidebonds between polypeptide units.
Role of Cysteine and Cystine in formation Covalentbonds stabilizingprotein structure
Cystine has disulfide (S-S) as a functional group . It is formed from Cystine
(Dicysteine)after oxidation. Cystine on reduction yields two Cysteine molecules.
Two Cysteineresidues can connect two polypeptide chains by formation of
Interchaindisulfidebondsor links. e.g. Keratin , Insulin
Cystine has disulfide (S-S) as a functional group . It is formed from Cystine
(Dicysteine)after oxidation. Cystine on reduction yields two Cysteine molecules.
Two Cysteineresidues can connect two polypeptide chains by formation of
Interchaindisulfidebondsor links. e.g. Keratin , Insulin
Intrachainand InterchainDisulfidebonds(S-S bonds) in Human Insulin
Carboxy-terminal end
A chain : Asparagine
B chain :Threonine
Amino-terminal end
A chain : Glycine
B chain : Phenylalanine
Apolypeptide chain :
21 amino acids
Bpolypeptide chain :
30 amino acids
intrachain disulphide bond :between
Cysteine residues( 6
th
amino acid of A
chain with11
th
amino acid of B chain)
interchain disulphide bonds
Carboxy-terminal end
A chain : Asparagine
B chain :Threonine
Amino-terminal end
A chain : Glycine
B chain : Phenylalanine
Apolypeptide chain :
21 amino acids
Bpolypeptide chain :
30 amino acids
intrachain disulphide bond :between
Cysteine residues( 6
th
amino acid of A
chain with11
th
amino acid of B chain)
interchain disulphide bonds
Classification Alpha-keratin structure based on Sulphur and disulphide bridges content
Type of keratinabundant in
structure
Sulphur and disulphide bridges content
Hardkeratin Hair, nails ,hornHighSulphur and disulphide bridges (rich
in cysteine residue) content
Softkeratin Skin LowSulphur and disulphide bridges (poor
in cysteine residue) content
➢Disulphide bonds are common in structural proteins like Keratin,
extracellular enzymes such as ribonucleasebut rare in Intracellular globular
proteins.
➢These bonds help to stabilize protein molecules against denaturation and
confer additionalstability them .
Type of keratinabundant in
structure
Sulphur and disulphide bridges content
Hardkeratin Hair, nails ,hornHighSulphur and disulphide bridges (rich
in cysteine residue) content
Softkeratin Skin LowSulphur and disulphide bridges (poor
in cysteine residue) content
➢Disulphide bonds are common in structural proteins like Keratin,
extracellular enzymes such as ribonucleasebut rare in Intracellular globular
proteins.
➢These bonds help to stabilize protein molecules against denaturation and
confer additionalstability them .
Importance of Disulphide bonds of Keratin structure in hair
•Springinessof hair is due to the characteristic coiledcoilstructuralmotif.
•When stretched , the coiled coil will untwist and resume the original
structure.
•Hairstyling/dressing: Stretching of hair using moist heat to break
disulphide bonds of keratin structure.
•Epidermolysisbullosa: abnormalities in keratin structure →loss of integrity
of skin
Hair styling Hair dressing / status of disulphide bond of keratin
Stretching hair stylingReduction of disulphide bonds of keratin to break these bonds
Curling hair stylingRe-oxidation of disulphide bonds of keratin to form new bonds
•Springinessof hair is due to the characteristic coiledcoilstructuralmotif.
•When stretched , the coiled coil will untwist and resume the original
structure.
•Hairstyling/dressing: Stretching of hair using moist heat to break
disulphide bonds of keratin structure.
•Epidermolysisbullosa: abnormalities in keratin structure →loss of integrity
of skin
Hair styling Hair dressing / status of disulphide bond of keratin
Stretching hair stylingReduction of disulphide bonds of keratin to break these bonds
Curling hair stylingRe-oxidation of disulphide bonds of keratin to form new bonds
Hair styling /dressing : Stretching of hair using moist heat to break disulphide
bonds of keratin structure
Hard keratin andSoft keratin
Stretching hair styling: Reduction of
disulphide bonds of keratin to break
these bonds
HighSulphur and disulphide bridges
(rich in cysteine residue) content
bonds of keratin structure
Hard keratin andSoft keratin
Stretching hair styling: Reduction of
disulphide bonds of keratin to break
these bonds
HighSulphur and disulphide bridges
(rich in cysteine residue) content
and -conformation of Keratin in Hair waving
Hair with -helices of -Keratin
-helices of -Keratin stretched →conformation of Keratin
conformation of Keratin reverted to -helices of -Keratin
cooling
exposedto moistheat
Hair with -helices of -Keratin
-helices of -Keratin stretched →conformation of Keratin
conformation of Keratin reverted to -helices of -Keratin
cooling
exposedto moistheat
Biochemical aspects of Hair curling(waving)
Hair to be curled is bent to appropriate shape
Disulfide bonds of Cystine are converted to sulfhydryl groups of Cysteine
Uncoiling of -helical structureof -Keratin
New Disulfide bonds are formed between Cysteine residues of keratin→altered -helical
structure of -Keratin
Hair with desired curls (temporary structure)
Growth of new hair with native conformation without curls
Application of reducing agents
Removal of reducing agents and addition of oxidizing agent
Hair washed and cooled
Hair to be curled is bent to appropriate shape
Disulfide bonds of Cystine are converted to sulfhydryl groups of Cysteine
Uncoiling of -helical structureof -Keratin
New Disulfide bonds are formed between Cysteine residues of keratin→altered -helical
structure of -Keratin
Hair with desired curls (temporary structure)
Growth of new hair with native conformation without curls
Application of reducing agents
Removal of reducing agents and addition of oxidizing agent
Hair washed and cooled
Alteration of Keratin structure in hair waving
I I I I I
S S S S S
I I I I I
S S S S S
I I I I I
I I I I I
SH SH SH SH SH
SH SH SH SH SH
I I I I I
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
S
S
S
S S
S
S
SSH
SH
S
S
Reduction
Curling
Oxidation
S
S
Schematic diagram
I I I I I
S S S S S
I I I I I
S S S S S
I I I I I
I I I I I
SH SH SH SH SH
SH SH SH SH SH
I I I I I
SH
SH
SH
SH
SH
SH
SH
SH
SH
SH
S
S
S
S S
S
S
SSH
SH
S
S
Reduction
Curling
Oxidation
S
S
Schematic diagram
Hairstyling/dressing
Hair curling(waving) Hairstraitening
Hair curling(waving) Hairstraitening
Non-covalent interactions in Tertiary structure of globular proteins
❖Tertiary structure of globular proteins : refers to the three-dimensional conformation of
proteins generated and maintained by weak bonds(valence forces)/non-covalent
interactions such as:
a.Hydrogenbonds: formed between -CO and NH-of two different peptide bonds or -OH
group of hydroxy amino acids(Serine etc.) and-COOH groups of acidic amino acids
Aspartic or Glutamic acid.
b.Ionicbonds/electrostaticinteractions/salt bridges :formed between oppositely charged
groups when they are in close vicinity . They are also formed oppositely charged R groups
of polar amino acid residues . e.g. basic (Histidine, Arginine , Lysine)and acidic amino
acids (Aspartic acid, Glutamic acid)
c.Hydrophilicinteractions: water loving groups are associated with water.
d.Hydrophobicinteractions: formed between hydrophobic groups (hydrocarbon like)of
amino acids like Alanine and Phenylalanine.
e.VanderWaalforces: weak ,but collectively contribute maximum towards the protein
structure.
➢Duringfoldingofglobularproteins (spherical/round),hydrophobic groups prefer to be
interior and Hydrophilic groups prefer to be on the surface of proteinmolecule.
➢The tertiary structure acquired by a native protein is always thermodynamically most
stable.
❖Tertiary structure of globular proteins : refers to the three-dimensional conformation of
proteins generated and maintained by weak bonds(valence forces)/non-covalent
interactions such as:
a.Hydrogenbonds: formed between -CO and NH-of two different peptide bonds or -OH
group of hydroxy amino acids(Serine etc.) and-COOH groups of acidic amino acids
Aspartic or Glutamic acid.
b.Ionicbonds/electrostaticinteractions/salt bridges :formed between oppositely charged
groups when they are in close vicinity . They are also formed oppositely charged R groups
of polar amino acid residues . e.g. basic (Histidine, Arginine , Lysine)and acidic amino
acids (Aspartic acid, Glutamic acid)
c.Hydrophilicinteractions: water loving groups are associated with water.
d.Hydrophobicinteractions: formed between hydrophobic groups (hydrocarbon like)of
amino acids like Alanine and Phenylalanine.
e.VanderWaalforces: weak ,but collectively contribute maximum towards the protein
structure.
➢Duringfoldingofglobularproteins (spherical/round),hydrophobic groups prefer to be
interior and Hydrophilic groups prefer to be on the surface of proteinmolecule.
➢The tertiary structure acquired by a native protein is always thermodynamically most
stable.
Properties of Hydrogenbonds responsible for protein structure
❖Properties of Hydrogenbonds responsible for protein structure:
•Hydrogen bondsare formed between NH-and –CO groups of peptide bonds
by sharing single hydrogen .
•Each Hydrogenbond is weak but collectively they are strong. A large number
of Hydrogenbonds significantly contribute stability to the protein structure.
•Hydrogen bondsmay be intrachain( between same polypeptide chain) or
interchain( between different polypeptide chains)
•Side chains of 11 out of 20 standard amino acids can participate in hydrogen
bonding (i.e. Tryptophan, Tyrosine , Aspartic acid, Asparagine ,Glutamic acid,
Glutamine , Histidine , Arginine , Serine , Threonine, Lysine).
•Formation of Hydrogenbonds between polarsidegroupson the surface of
protein enhancessolubilityof the protein.
❖Properties of Hydrogenbonds responsible for protein structure:
•Hydrogen bondsare formed between NH-and –CO groups of peptide bonds
by sharing single hydrogen .
•Each Hydrogenbond is weak but collectively they are strong. A large number
of Hydrogenbonds significantly contribute stability to the protein structure.
•Hydrogen bondsmay be intrachain( between same polypeptide chain) or
interchain( between different polypeptide chains)
•Side chains of 11 out of 20 standard amino acids can participate in hydrogen
bonding (i.e. Tryptophan, Tyrosine , Aspartic acid, Asparagine ,Glutamic acid,
Glutamine , Histidine , Arginine , Serine , Threonine, Lysine).
•Formation of Hydrogenbonds between polarsidegroupson the surface of
protein enhancessolubilityof the protein.
Structure of interchain Hydrogen bonds
H O H
I II I Schematic diagram
N C N
C N C
II I II
O H O
H H O
C I N C
II N C N
O II I
O H
interchain Hydrogen bond
III
H O H
I II I Schematic diagram
N C N
C N C
II I II
O H O
H H O
C I N C
II N C N
O II I
O H
interchain Hydrogen bond
III
Hydrogen donor and Hydrogen acceptor in Hydrogenbonds
responsible for protein structure
❖Hydrogenbonds responsible for protein structure: are weak electrostatic
interactions between one electronegative atom like O or N and hydrogen
atom linked to second electronegative atom .
Group of Hydrogen donor Hydrogen donor
-NH Imidazole , indole ,peptide
-OH Serine ,Threonine
Group of Hydrogen acceptor Hydrogen acceptor
COO
-
Aspartic acid ,Glutamic acid
C=O Peptide
-S-S- Disulphide
responsible for protein structure
❖Hydrogenbonds responsible for protein structure: are weak electrostatic
interactions between one electronegative atom like O or N and hydrogen
atom linked to second electronegative atom .
Group of Hydrogen donor Hydrogen donor
-NH Imidazole , indole ,peptide
-OH Serine ,Threonine
Group of Hydrogen acceptor Hydrogen acceptor
COO
-
Aspartic acid ,Glutamic acid
C=O Peptide
-S-S- Disulphide
Hydrophobic bonds responsible for protein structure
❖Hydrophobicbondsin protein structure :
➢are formed by interactions between HydrophobicR groups(non-polar side
chains) of neutral amino acids like Alanine , Valine , Leucine, Isoleucine,
Methionine, Phenylalanine , Tryptophan by eliminating water molecules.
➢arenottruebonds.
➢serves to hold lipophilic side chains together.
➢The occurrence of hydrophobic forces is observed in aqueous environment
wherein the molecules are forced to stay together.
❖Hydrophobicbondsin protein structure :
➢are formed by interactions between HydrophobicR groups(non-polar side
chains) of neutral amino acids like Alanine , Valine , Leucine, Isoleucine,
Methionine, Phenylalanine , Tryptophan by eliminating water molecules.
➢arenottruebonds.
➢serves to hold lipophilic side chains together.
➢The occurrence of hydrophobic forces is observed in aqueous environment
wherein the molecules are forced to stay together.
Hydrophobicinteractions
I
I
I
NH-CH-CO
HC-CH
3
CH
2
CH
3
H
3CCH
3
CH
CH
2
NH-CH-CO
I
I
Leucine
Isoleucine
Hydrophobicinteractions:
1.non-polar side chains of neutral
amino acids tend to be closely
associated with each other in
protein confirmation.
2.are Nottruebonds.
3.Observed in aqueous
environment wherein the
molecules are forced to stay
together.
Schematic diagram
I
I
I
NH-CH-CO
HC-CH
3
CH
2
CH
3
H
3CCH
3
CH
CH
2
NH-CH-CO
I
I
Leucine
Isoleucine
Hydrophobicinteractions:
1.non-polar side chains of neutral
amino acids tend to be closely
associated with each other in
protein confirmation.
2.are Nottruebonds.
3.Observed in aqueous
environment wherein the
molecules are forced to stay
together.
Schematic diagram
Electrostaticbonds:Bonds responsible for protein structure
Electrostatic/ionic/ saltbonds/salt bridges: formed between oppositely charged
groups when they are in close vicinity i.e. negatively charged group linked to positively
charged group of amino acid e.g. COO ⁻ of Glutamic acid associates with NH₃⁺of
Lysine. They are also formed oppositely charged R groups of polar amino acid residues.
Positive charges contributed by : epsilon amino group of lysine , guanidium group of Arginine,
imidazole group of Histidine
Negative charges contributed by : beta and gamma carboxyl group of Aspartic acid and
Glutamic acid respectively
Electrostatic/ionic/ saltbonds/salt bridges: formed between oppositely charged
groups when they are in close vicinity i.e. negatively charged group linked to positively
charged group of amino acid e.g. COO ⁻ of Glutamic acid associates with NH₃⁺of
Lysine. They are also formed oppositely charged R groups of polar amino acid residues.
Positive charges contributed by : epsilon amino group of lysine , guanidium group of Arginine,
imidazole group of Histidine
Negative charges contributed by : beta and gamma carboxyl group of Aspartic acid and
Glutamic acid respectively
Electrostatic interactions
NH-CH-CO
CH
C
O O
-
N
+
H
3
(CH
2)
4
NH-CH
2-CO
Schematic diagram
Aspartate:acidicaminoacid
Lysine:basic amino acid
❖Electrostaticinteractions:
are formed between
negatively charged groups
( e.g. COO
-
)of acidic amino
acidwith positively charged
groups (e.g. -N
+
H
3) of basic
amino acid.
❖They are also formed
oppositely charged R
groups of polar amino acid
residues.
Electrostaticinteractions→
I
I
I
I
NH-CH-CO
CH
C
O O
-
N
+
H
3
(CH
2)
4
NH-CH
2-CO
Schematic diagram
Aspartate:acidicaminoacid
Lysine:basic amino acid
❖Electrostaticinteractions:
are formed between
negatively charged groups
( e.g. COO
-
)of acidic amino
acidwith positively charged
groups (e.g. -N
+
H
3) of basic
amino acid.
❖They are also formed
oppositely charged R
groups of polar amino acid
residues.
Electrostaticinteractions→
I
I
I
I
Van Der Waals forces: Bonds responsible for protein structure
❖Van Der Waals forces/interactions :Electrically neutral molecules associate by
electrostatic interactions due to inducedipoles.
❖CharacteristicsofVan Der Waals forces/interactions :
•are the non-covalent associations.
•are very weak ,but collectively contribute maximum towards the protein
structure.
•act only on short distances.
•include both an attractive and repulsive component between both polar and
non-polar side chain of amino acid residues.
❖Van Der Waals forces/interactions :Electrically neutral molecules associate by
electrostatic interactions due to inducedipoles.
❖CharacteristicsofVan Der Waals forces/interactions :
•are the non-covalent associations.
•are very weak ,but collectively contribute maximum towards the protein
structure.
•act only on short distances.
•include both an attractive and repulsive component between both polar and
non-polar side chain of amino acid residues.
Van Der Waals forces : Bonds responsible for protein structure
Van Der Waals forces/interactions : Electrically neutral molecules associate by
electrostatic interactions due to induce dipoles. These are the non-covalent associations.
They are very weak ,but collectively contribute maximum towards the protein structure.
They act only on short distances. They include both an attractive and repulsive component
between both polar and non-polar side chain of amino acid residues.
inducedipole
Van Der Waals forces/interactions : Electrically neutral molecules associate by
electrostatic interactions due to induce dipoles. These are the non-covalent associations.
They are very weak ,but collectively contribute maximum towards the protein structure.
They act only on short distances. They include both an attractive and repulsive component
between both polar and non-polar side chain of amino acid residues.
inducedipole
Factors stabilizing the tertiary structure of Globular proteins
A B C D C=O S N
O
-
H
E F G H N
+
H
3 S O
Ionicinteractions
CovalentCysteineinterlinks
Association of hydrophobic R groups within molecule,
shielded from water
Hydrogenbonds
Schematic diagram
A B C D C=O S N
O
-
H
E F G H N
+
H
3 S O
Ionicinteractions
CovalentCysteineinterlinks
Association of hydrophobic R groups within molecule,
shielded from water
Hydrogenbonds
Schematic diagram
Weak bonds stabilizing Tertiary structure of proteins
PeptidebondSerineLysineAlaninePhenylalanine Cysteine
NH CH
2OH N
+
H
3CH
3 S
O O
-
O C=O C=O CH
3 S
C
PeptidebondAsp AspAlaninePhenylalanine Cysteine
Hydrogenbonds ionicbond hydrophobicinteractionsdisulfidebond
=
Tertiary structure of a native protein denotes overall arrangement and inter-relationship of various regions or
domains of single polypeptide chain .It is thermodynamically the most stable conformation.
Schematic diagram
PeptidebondSerineLysineAlaninePhenylalanine Cysteine
NH CH
2OH N
+
H
3CH
3 S
O O
-
O C=O C=O CH
3 S
C
PeptidebondAsp AspAlaninePhenylalanine Cysteine
Hydrogenbonds ionicbond hydrophobicinteractionsdisulfidebond
=
Tertiary structure of a native protein denotes overall arrangement and inter-relationship of various regions or
domains of single polypeptide chain .It is thermodynamically the most stable conformation.
Schematic diagram
Domains of globularproteins
❖Domainsof globularprotein:
➢The term domainis used to represent the basic structural and functional units of
protein with tertiary structure(denotes a compact globular functional unit of
protein).
➢Relatively independent region and may represent a functional unit.
➢are usually connected with relatively flexible areas of protein (e.g. immunoglobulin)
❖3 Domains of Phenylalanine hydroxylase :
a.Catalytic
b.Regulatory
c.Protein-protein interaction domain
❖Calmodulin: a calcium binding regulatory protein(regulates intracellular calcium
levels )
❖A polypeptide with 200 amino acids normally consists of two or more domains.
❖Domainsof globularprotein:
➢The term domainis used to represent the basic structural and functional units of
protein with tertiary structure(denotes a compact globular functional unit of
protein).
➢Relatively independent region and may represent a functional unit.
➢are usually connected with relatively flexible areas of protein (e.g. immunoglobulin)
❖3 Domains of Phenylalanine hydroxylase :
a.Catalytic
b.Regulatory
c.Protein-protein interaction domain
❖Calmodulin: a calcium binding regulatory protein(regulates intracellular calcium
levels )
❖A polypeptide with 200 amino acids normally consists of two or more domains.
Domains of globularproteinsimmunoglobulins and Phenylalanine hydroxylase
Domains of immunoglobulinsare usually
connected with relatively flexible areas of protein.
3 Domains of Phenylalanine hydroxylase : Catalytic,
Regulatory, Protein-protein interaction domain
Domains of immunoglobulinsare usually
connected with relatively flexible areas of protein.
3 Domains of Phenylalanine hydroxylase : Catalytic,
Regulatory, Protein-protein interaction domain
Domains of Calmodulin: a calcium binding regulatory protein
Domains of
Calmodulin
Domains of
Calmodulin
Domains of ribonuclease
Domains of ribonuclease :catalytic and RNA binding domain to facilitate its function of
cleavage of ribonucleic acids(RNA)
Domains of ribonuclease :catalytic and RNA binding domain to facilitate its function of
cleavage of ribonucleic acids(RNA)
Quaternary structure of globular proteins :
refers to the spatial arrangement of
subunits (polypeptide chains) linked by non-
covalent interactions in protein molecule .
refers to the spatial arrangement of
subunits (polypeptide chains) linked by non-
covalent interactions in protein molecule .
Quaternary structure of globular proteins:1
❖A number of proteins are made up of with two or more peptide chains(subunits/
monomers/ protomers)which may be identical or unrelated. Such proteins are
termed as oligomers. Subunits of oligomers are not covalently linked(non-covalent
forces). This association of subunits to form protein molecule is known as
Quaternary structure. Not all proteins are polymeric.
✓Globular proteins loose their functions on dissociation of subunits.
❖Forces involved to aggregate subunits :
a.Hydrogenbonds
b.Ionic/electrostaticinteractions
c.Hydrophobicinteractions
d.Van der Waal forces
➢The same weak bonds are involved in secondary and tertiary structure in this
associations.
❖A number of proteins are made up of with two or more peptide chains(subunits/
monomers/ protomers)which may be identical or unrelated. Such proteins are
termed as oligomers. Subunits of oligomers are not covalently linked(non-covalent
forces). This association of subunits to form protein molecule is known as
Quaternary structure. Not all proteins are polymeric.
✓Globular proteins loose their functions on dissociation of subunits.
❖Forces involved to aggregate subunits :
a.Hydrogenbonds
b.Ionic/electrostaticinteractions
c.Hydrophobicinteractions
d.Van der Waal forces
➢The same weak bonds are involved in secondary and tertiary structure in this
associations.
Quaternary structure of globular proteins:2
❖Quaternary structure of globular proteins:refers to the spatial arrangement of
subunits (polypeptidechains)linked by non-covalent interactions in three
dimensional complexes. It occurs in proteins with two or more peptide chains. .
❖Monomeror promoter or subunits:Individual polypeptide chain of oligomeric
protein
•Monomersin Quaternary structure of globular proteinsstabilized by
a.Hydrogen bonds
b.Hydrophobic interactions non-covalent bonds
c.Ionic bonds /electrostatic interactions/salt bridges
d.Van der Waals forces
❖Dimer: 2 polypeptide chains (e.g. Insulin)
❖Tetramers: 4 polypeptide chains (e.g. LDH ,Hemoglobin ,SGOT)
❖Oligomers: proteins with 2 or more polypeptides chain
❖Quaternary structure of globular proteins:refers to the spatial arrangement of
subunits (polypeptidechains)linked by non-covalent interactions in three
dimensional complexes. It occurs in proteins with two or more peptide chains. .
❖Monomeror promoter or subunits:Individual polypeptide chain of oligomeric
protein
•Monomersin Quaternary structure of globular proteinsstabilized by
a.Hydrogen bonds
b.Hydrophobic interactions non-covalent bonds
c.Ionic bonds /electrostatic interactions/salt bridges
d.Van der Waals forces
❖Dimer: 2 polypeptide chains (e.g. Insulin)
❖Tetramers: 4 polypeptide chains (e.g. LDH ,Hemoglobin ,SGOT)
❖Oligomers: proteins with 2 or more polypeptides chain
Examples of proteins(oligomers) having quaternary structure
❖Examples of proteins having quaternary structure :
•Hemoglobin
•Creatine kinase
•Alkaline phosphatase
•Glycolyticenzymes:
a.Aldolase
b.Lactate dehydrogenase
c.Pyruvate dehydrogenase
❖Examples of proteins having quaternary structure :
•Hemoglobin
•Creatine kinase
•Alkaline phosphatase
•Glycolyticenzymes:
a.Aldolase
b.Lactate dehydrogenase
c.Pyruvate dehydrogenase
Types of globular protein based on number of constituent polypeptide chains
Type Componentpolypeptide chains as functional unit Exampleofglobularprotein
Dimer 2 polypeptide chains Creatine kinase (CK)
Homodimercontains 2 copies of the same polypeptide chain
→2 Alpha()chains +2 Beta()chains
Hemoglobin
Heterodimercontains 2 different types the polypeptides as a
functional unit →with A and B polypeptide chains
Insulin
Tetramer4 polypeptide chains ( H and M type polypeptide
chains 2 each )
Lactate dehydrogenase
(LDH)
Tetramer4 polypeptide chains ( light and heavy chains
polypeptidechains 2 each )
Immunoglobulin G
Type Componentpolypeptide chains as functional unit Exampleofglobularprotein
Dimer 2 polypeptide chains Creatine kinase (CK)
Homodimercontains 2 copies of the same polypeptide chain
→2 Alpha()chains +2 Beta()chains
Hemoglobin
Heterodimercontains 2 different types the polypeptides as a
functional unit →with A and B polypeptide chains
Insulin
Tetramer4 polypeptide chains ( H and M type polypeptide
chains 2 each )
Lactate dehydrogenase
(LDH)
Tetramer4 polypeptide chains ( light and heavy chains
polypeptidechains 2 each )
Immunoglobulin G
Quaternary structure of Hemoglobin
Hemoglobin (HbA1)has
4 Polypeptides chains
(tetramer) associated by
non-covalent bonds :
2 Alpha()chains
+
2 Beta()chains
It possessesQuaternary
structure(oligomeric).
In this , R group contacts are
present between similar side
chains and there is very little
contact between dissimilar
side chains.
HbA:
Tetramer
2
2
Each chain has one heme
group and so one Fe
2+
ion
Hemoglobin (HbA1)has
4 Polypeptides chains
(tetramer) associated by
non-covalent bonds :
2 Alpha()chains
+
2 Beta()chains
It possessesQuaternary
structure(oligomeric).
In this , R group contacts are
present between similar side
chains and there is very little
contact between dissimilar
side chains.
HbA:
Tetramer
2
2
Each chain has one heme
group and so one Fe
2+
ion
Importance of Quaternary structure of globular proteins
❖Importance of Quaternary structure of globular proteins :
1.Subunits of oligomeric proteins may either function independently of each
other or may work cooperatively as in Hemoglobin where the binding of
oxygen to one subunit of tetramer increases the affinity of other subunits
for oxygen.
2.Oligomeric proteins are regulators of cell metabolism & cellular functions.
❖Importance of Quaternary structure of globular proteins :
1.Subunits of oligomeric proteins may either function independently of each
other or may work cooperatively as in Hemoglobin where the binding of
oxygen to one subunit of tetramer increases the affinity of other subunits
for oxygen.
2.Oligomeric proteins are regulators of cell metabolism & cellular functions.
Deoxy –Hb HbO₂ Hb O₄ Hb O₆ Hb O₈
T form ↓ ↓ ↓ ↓ ↓
↑
R form
Oxygenation of Hemoglobin
Quaternary structure of Hemoglobin favors its functions :Binding of oxygen(O
2) to
one heme unit facilitates oxygen binding by other subunits.
T form ↓ ↓ ↓ ↓ ↓
↑
R form
Oxygenation of Hemoglobin
Quaternary structure of Hemoglobin favors its functions :Binding of oxygen(O
2) to
one heme unit facilitates oxygen binding by other subunits.
Four levels of structural organization of proteins
The overall conformation of a protein , the particular position of the amino acid chains in three dimensional
space determines the function/s of the protein.
The overall conformation of a protein , the particular position of the amino acid chains in three dimensional
space determines the function/s of the protein.
Four levels of structural organization of proteins
Many geneticdiseasesresult from protein with abnormalaminoacidsequences. If the
primary structureofthenormalandmutatedproteins are known , this information may be
used to diagnoseor clinical study of the disease.
Many geneticdiseasesresult from protein with abnormalaminoacidsequences. If the
primary structureofthenormalandmutatedproteins are known , this information may be
used to diagnoseor clinical study of the disease.
Tags
four levels of protein structure
characteristics of primary structure of proteins
characteristics of alpha-helix
right and left-handed alpha-helix
characteristics of beta-pleated sheet
comparison of alpha-helix and beta-pleated sheet
parallel and anti-parallel beta- pleated sheet
disordered region and its importance
super secondary structures of proteins
protein motifs
tertiary structure of proteins
importance of disulphide bonds of keratin structur
hair styling dressing
and -conformation of keratin in hair waving
biochemical aspects of hair curling waving
alteration of keratin structure in hair waving
domains of globular proteins immunoglobulins and p
quaternary structure of hemoglobin favors its func
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