Lecture 1.ppt protien structure in laboratory department

Prituen structure

1. ProteinsProteins: The primary worker : The primary worker
molecule in the bodymolecule in the body
•Transport- hemoglobin in blood
•Storage- ferritin in liver
•Immune response- antibodies
•Receptors- sense stimuli, e.g. in neurons
•Channels- control cell contents
•Structure- collagen in skin
•Enzymes- catalyze biochemical reactions
•Cell functions- multi-protein machines

2. Proteins:
• Proteins are biopolymers (called polypeptides) of L-amino acids.
• Amino acids in proteins are joined to each other via peptide bonds.
• Only L-amino acids are used to make proteins (rare exceptions of
proteins in bacterial cell wall, which contain some D-amino acids).
• The process of putting amino acids together to make proteins is
called translation.
• Translation relies on the genetic code, in which three nucleotides
in mRNA specify one amino acid in protein.

4. The synthesis of a polymer

5. The Breakdown of a polymer

6. Proteins are amino acid polymersProteins are amino acid polymers
•20 different amino acids: many combinations
•Proteins are made in the RIBOSOME

7. Amino acid: Basic unit of proteinAmino acid: Basic unit of protein
COO
-
NH
3
+
C
R
H
An amino
acid
Different side
chains, R, determine
the properties of 20
amino acids.
Amino group Carboxylic
acid group

8. Uses of Amino Acids
Protein Synthesis: The synthesis of new proteins is very important
during growth. In adults new protein synthesis is directed towards
replacement of proteins as they are constantly turned over.
Synthesis of variety of other compounds:
Purines and Pyrimidines (Compounds of nucleotides)
Catecholamines (Adrenaline and Noradrenaline)
Neurotransmitters
Histamine
Porphyrins (The central oxygen binding component of hemoglobin)
As biological fuel:
About 10 percent of the energy production in humans is from amino acids.
The percentage is higher in carnivores whose diet is almost entirely
proteins.

9. Classification of amino acids according to the chemical
properties of R side chains:

10. Essential & Non Essential Amino Acids
About half of the 20 amino acids needed by humans cannot be
synthesized at a rapid enough rate to support growth; they
must be supplied in food.
These nutritionally essential amino acids must be supplied by
the diet in the form of proteins. The essential amino acids are
arginine (often called semiessential as it is required for the
young but not for adults and can be synthesized in high enough
amounts that the body needs), histidine, isoleucine, leucine,
lysine, methionine, phenylalanine, threonine, tryptophan, and
valine.
The 10 amino acids that the body can produce are alanine,
asparagine, aspartic acid, cysteine, glutamic acid, glutamine,
glycine, proline, serine, and tyrosine. Tyrosine is produced from
phenylalanine, so if the diet is deficient in phenylalanine,
tyrosine will be required as well. Humans do not have all the
enzymes required for the biosynthesis of all of the amino acids.

11. Nutritional or Biological classification:
•Prokaryotes such as E-Coli can make the carbon skeleton of all the 20
amino acids BUT humans cannot synthesize the branched carbon chains
found in the branched chain amino acids, OR the ring system found in the
phenylalanine and the aromatic amino acids, nor can we incorporate
sulphur into covalently bonded structures.
 
•Reason thereof the NINE so called Essential Amino Acids must be supplied
in the diet and the remaining 11 amino acids are non essential i.e. they
can be synthesized inside the body from the TCA cycle intermediates and
other metabolic pathways.

13. Metabolic classification of amino acids:
 
•The degradation of carbon skeleton follows one of the following pathways.
•Ketogenic amino acids: They produce Acetyl CoA or Acetoacetate that can be
used in the formation of ketone bodies.
•Glucogenic amino acids: They produce Alpha KG or any intermediate of TCA
cycle that can be used for glucose synthesis.
•Mixed: Glucogenic and Ketogenic, they give both glucose and ketone bodies.
•
Degradation of amino acids starts by degradation of amino group.

14. Glucogenic / Ketogenic Amino Acids
Amino acids are grouped into two classes, based on whether or not
their carbon skeletons can be converted to glucose.
Glucogenic Amino Acids: Carbon skeletons are degraded to pyruvate
or to one of the (4) or (5) carbon intermediates of Krebs-Cycle that are
precursors for gluconeogenesis.

(Gluconeogenesis is a central metabolic pathway involving
biosynthesis of the sugar glucose. One starting point for
gluconeogenesis is two molecules of pyruvate and the process ends
with formation of one glucose molecule.)
Glucogenic amino acids are the major carbon source for
gluconeogenesis when glucose levels are low. They can be also
catabolized for energy or converted to glycogen or fatty acids for
energy storage.

15. Ketogenic Amino Acids
Their carbon skeletons are degraded to acetyl-
CoA and/or acetoacetate. For every acetyl
residue entering Krebs cycle, two carbon atoms
leave as CO
2. Carbon skeleton of ketogenic
amino acids can be converted for energy in
Krebs Cycle or converted to ketone bodies or
fats.
Note: They cannot be converted to glucose.

16. FATE OF THE CARBON
SKELETONS
Carbon skeletons are used for
energy.
Glucogenic: TCA cycle
intermediates
or pyruvate
(gluconeogensis)
Ketogenic: acetyl CoA, acetoacetyl
CoA,
or acetoacetate

18.  amino N-terminus
 carboxyl C-terminus

19. Making a polypeptide chain
Amino acid covalent bond and peptide bond

20. Amino Acid ChemistryAmino Acid Chemistry
NH2C

R
1
CO
H
NHC

R
2
COOH
H
NH2C

R
COOH
H
amino acid
20 different types
Amino acid Polypeptide Protein
NH2C

R
1
COOH
H
NH2C

R
2
COOH
H

21. Amino Acid ChemistryAmino Acid Chemistry
NH2C

R
COOH
H
amino acid
The free amino and carboxylic acid groups have pKa’s
COOH
COO
-
pKa ~ 2.2
NH2NH3
+
pKa ~ 9.4
At physiological pH, amino acids are zwitterions
+
NH3C

R
COO
-
H

22. Amino Acids: Zwitterions
Amino acids can exist as
zwitterions - substances
containing equal
numbers of positive and
negative charge. Due to
their carboxyl and amine
groups, which can be
negatively and positively
charged, respectively.

23. Peptide Bonds
L- amino acids are the building blocks of proteins.
There are twenty different L- amino acids, but only one bond, the peptide
bond, is used to join them together.
Peptide bonds form in the process of translation when the -amino group of
one amino acid residue forms a covalent bond with the -carboxyl group of
another amino acid residue resulting in the elimination of water.

24. Formation of a peptide.

25. Proteins are linear polymers of amino Proteins are linear polymers of amino
acidsacids
R
1
NH
3
＋
CCO
H
R
2
NHCCO
H
R
3
NHCCO
H
R
2
NH
3
＋
CCOO
ー
H
＋
R
1
NH
3
＋
CCOO
ー
H
＋
H
2
OH
2
O
Peptide
bond
Peptide
bond
The amino acid
sequence is called as
primary structure
A A
F
N
G
G
S
T
S
D
K
A carboxylic acid
condenses with an
amino group with the
release of a water

26. Amino acid sequence is encoded by Amino acid sequence is encoded by
DNA base sequence in a geneDNA base sequence in a gene
・
C
G
C
G
A
A
T
T
C
G
C
G
・
・
G
C
G
C
T
T
A
A
G
C
G
C
・
DNA molecule
＝
DNA base
sequence

27. Hierarchical nature of protein Hierarchical nature of protein
structurestructure
Primary structure (Amino acid sequence)
↓
Secondary structure （α-helix, β-sheet）
↓
Tertiary structure （Three-dimensional structure
formed by assembly of secondary structures）
↓
Quaternary structure （Structure formed by more
than one polypeptide chains）

28. The primary structure
of a protein
This is the number, type, and sequence of
amino acid in the polypeptide chain.

29. •Secondary Structure: Twisting or folding of
polypeptide chain to form regular, non
random repeating structure e.g. alpha helix
“-Helix” and Beta pleated sheets “-sheets”.

30. •-Helix: Spiral structure consisting of tightly packed, coiled polypeptide
backbone core.
•The side chains of amino acid extend outward from the axis of the helix.
•-Helix is stabilized by hydrogen bonds
•Each turn of the helical structure contains 3.6 amino acids.
•-Helix is right to left-handed.
•Alpha helix is disrupted by some amino acids:
•Proline: because of its imino group.
•Charged amino acids
•Bulky amino acids e.g. Valine, Leucine, Isoleucine, Tryptophan.

31. •-Pleated sheets:
•It is a non random structure of protein in which the polypeptide chains
line side-by-side forming sheets.
•The structure in beta sheets is stabilized by hydrogen bonds. These
hydrogen bonds maybe:
–Interchain: formed between amino acids of different or separated
polypeptide chains.
–Intrachain: formed between amino acids of same polypeptide chains.
•Beta sheets can be formed by single chain back on itself or maybe formed
between two or more polypeptide chains that are arranged either parallel
or antiparallel.

32. The alpha helix and beta sheet.

33. Tertiary structure of a protein
It is the three dimensional
structure formed by the assembly
of secondary structures.
The three dimensional structure of
protein is related to the function of
protein and any alteration in its
conformation will affect protein
function.
Every protein has a unique tertiary
structure made up of secondary
structure element i.e. Helices and
Beta sheets.
Example: Myoglobin: 75 % of
Myoglobin is alpha helix

34. Quaternary Structure
Quaternary structure of protein exists for proteins, which are made up
of more than one subunit.
Example: Hemoglobin is a tetramer protein formed of four polypeptide
chains and Lactate dehydrogenase is also a tetramer protein.
The subunits are usually held by non covalent bonds (hydrophobic
interactions, Hydrogen and Ionic bonds).

35. The four levels of protein structure

36. The overall shape of protein
The two major classes of proteins are the fibrous proteins and the
globular proteins.
Fibrous proteins
Fibrous proteins are distinguished from globular proteins by their filamentous,
elongated form. Most of them play structural roles in animal cells and tissues,
holding things together.
Fibrous proteins have amino acid sequences that favor a particular kind of
secondary structure which, in turn, confer particular mechanical properties on
the proteins.
They have relatively high abundance of amino acids with non-bulky side chains,
such as glycine, alanine, serine, glutamate, and glutamine.

37. Globular Proteins
Globular proteins perform most of the chemical "work" of the cell
- synthesis, transport, and catabolism. They are folded into
compact structures very unlike the extended, filamentous forms of
the fibrous proteins.
Globular proteins illustrate the concept of tertiary structure -
which arises from folding of the polypeptide chain upon itself.
Unlike secondary structure, which is caused by interactions
between amino acids close to each other, tertiary structures are
seen to be stabilized by interactions between amino acids that are
often far apart.