Amino acids-Classification, Structure, and reactions of amino acids.pdf

Notes

1. Amino acids-Classification, Structure, and
reactions of amino acids
1

2. •Aminoacidsareorganiccompoundsthatserveasthebuildingblocksofproteins.
•Proteins,inturn,areessentialmacromoleculesthatplayacrucialroleinthestructureandfunction
oflivingorganisms.
•Aminoacidsarecharacterizedbythepresenceofbothamino(-NH2)andcarboxyl(-COOH)
functionalgroups,alongwithasidechain(Rgroup)thatvariesamongdifferentaminoacids.
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3. 3

4. •AminoGroup(-NH2):Thisgroupconsistsofanitrogenatombondedtotwohydrogenatoms.It
impartsbasicpropertiestotheaminoacid.
•CarboxylGroup(-COOH):Thisgroupiscomposedofacarbonatomdouble-bondedtoanoxygen
atomandsingle-bondedtoahydroxylgroup(-OH).Itgivestheaminoacidacidicproperties.
•SideChain(RGroup):Thesidechainisavariablegroupthatdistinguishesdifferentaminoacids.
•Itcanrangefromasinglehydrogenatomtocomplexstructures.
•Thenatureofthesidechaininfluencestheaminoacid'sproperties.
4

5. Early Discoveries:
•Asparagine(1806):
•DiscoveredbyFrenchchemistLouisNicolasVauquelininasparagusjuice.
•Namedafterasparagus,whereitwasfirstidentified.
•GlutamicAcid(1865):
•GermanchemistKarlHeinrichRitthausenisolatedglutamicacidfromwheatgluten.
•Namedforitsroleintheacidichydrolysisofgluten.
•CystineandCysteine(1810-1899):
•Cystine,adimerofcysteine,wasisolatedfromurinarycalculibyWilliamHydeWollastonin1810.
•ThestructureofcysteinewasdeterminedbyEmilFischerin1899.
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6. Classification of Amino Acids
•Non-polar, aliphatic amino acids:
•Glycine (Gly)
•Alanine (Ala)
•Valine (Val)
•Leucine (Leu)
•Isoleucine (Ile)
•Methionine (Met)
•Proline (Pro)
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7. 7

8. 8

9. •Polar, uncharged amino acids:
•Serine (Ser)
•Threonine (Thr)
•Cysteine (Cys)
•Asparagine (Asn)
•Glutamine (Gln)
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10. 10

11. 11

12. •Aromatic amino acids:
•Phenylalanine (Phe)
•Tyrosine (Tyr)
•Tryptophan (Trp)
12

13. •Positively charged (basic) amino acids:
•Lysine (Lys)
•Arginine (Arg)
•Histidine (His)
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14. •Negativelycharged(acidic)aminoacids:
•Asparticacid(Asp)
•Glutamicacid(Glu)
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15. 15

16. •Aminoacidsareclassifiednutritionallybasedontheiressentiality,meaningwhetherthehuman
bodycansynthesizethemendogenously(non-essential)oriftheymustbeobtainedthroughthe
diet(essential).
•Thisnutritionalclassificationisimportantforunderstandingdietaryrequirementsandensuringthat
thebodyreceivesanadequatesupplyofallessentialaminoacids.
•Theclassificationincludesthreemaincategories:essential,non-essential,andconditionally
essentialaminoacids.
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17. •EssentialAminoAcids:
•Theseaminoacidscannotbesynthesizedbythehumanbodyinsufficientamounts,sotheymust
beobtainedfromthediet.Therearenineessentialaminoacids:
•Isoleucine(Ile):
•Importantformusclemetabolism,immunefunction,andenergyregulation.
•Leucine(Leu):
•Playsakeyroleinproteinsynthesis,musclerepair,andgrowth.
•Lysine(Lys):
•Essentialforproteinsynthesis,collagenformation,andcalciumabsorption.
•Methionine(Met):
•Precursortootheraminoacids;involvedinmetabolismandantioxidantdefense.
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18. •Phenylalanine(Phe):
•Essentialforthesynthesisofneurotransmittersandotherimportantmolecules.
•Threonine(Thr):
•Necessaryfortheformationofproteins,collagen,andelastin.
•Tryptophan(Trp):
•Precursortoserotoninandmelatonin;importantformoodandsleepregulation.
•Valine(Val):
•Involvedinmusclemetabolism,tissuerepair,andenergyproduction.
•Histidine(His):
•Importantforthegrowthandrepairoftissues;aprecursortohistamine.
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19. •Non-essentialAminoAcids:
•Thehumanbodycansynthesizetheseaminoacids,sotheyarenotstrictlyrequiredinthediet.
•However,theirsynthesismaynotalwaysbesufficientundercertainconditionssuchasillnessor
stress.Thereareelevennon-essentialaminoacids:
•Alanine(Ala):
•Importantforglucoseproductionandenergymetabolism.
•Arginine(Arg):
•Involvedinimmunefunction,hormonerelease,andbloodvesselrelaxation.
•Asparagine(Asn):
•Importantforthesynthesisofproteinsandnucleotides.
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20. •AsparticAcid(Asp):
•Involvedintheureacycle,whichhelpseliminateammoniafromthebody.
•Cysteine(Cys):
•Aprecursortoantioxidantmolecules;importantforskinandhairhealth.
•GlutamicAcid(Glu):
•Functionsasaneurotransmitterandisinvolvedincellularmetabolism.
•Glutamine(Gln):
•Importantforimmunefunctionandmaintaininggutintegrity.
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21. •Glycine(Gly):
•Importantforthesynthesisofproteins,DNA,andRNA.
•Proline(Pro):
•Involvedincollagensynthesisandmaintainingskinelasticity.
•Serine(Ser):
•Importantforthesynthesisofproteins,nucleotides,andotheraminoacids.
•Tyrosine(Tyr):
•Precursortoneurotransmitters;importantforthesynthesisofhormones.
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22. •ConditionallyEssentialAminoAcids:
•Theseaminoacidsaretypicallyconsiderednon-essentialbecausethebodycansynthesizethem.
•However,undercertainconditions,thebody'sabilitytoproducethemmaybecompromised,
makingthemconditionallyessential.
•Examplesinclude:
•Arginine(Arg):
•Incertainsituations,suchasduringgrowth,illness,ortrauma,thebody'sabilitytoproduce
argininemaybeinsufficient.
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23. •Cysteine(Cys):
•Duringcertainconditions,suchasoxidativestressorillness,cysteinemaybecomeconditionally
essential.
•Tyrosine(Tyr):
•Insituationswherethereisalimitedsupplyofphenylalanine,asseeninphenylketonuria(PKU),
tyrosinemaybecomeconditionallyessential.
•Understandingthenutritionalclassificationofaminoacidsiscrucialfordesigningbalanceddiets
thatprovidethenecessarybuildingblocksforproteinsynthesisandoverallhealth.
•Avariedandbalanceddietthatincludesadiverserangeofproteinsourcestypicallyensuresan
adequatesupplyofbothessentialandnon-essentialaminoacids.
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24. Reactions of amino acids
•Aminoacidsparticipateinvariousbiochemicalreactions,contributingtoessentialprocessesinliving
organisms.Herearesomekeyreactionsinvolvingaminoacids:
•PeptideBondFormation:
•Reaction:Condensationreactionbetweentheaminogroupofoneaminoacidandthecarboxylgroup
ofanother,formingapeptidebond.
•Catalyst:Ribosomesandenzymescalledpeptidyltransferases.
•Importance:Peptidebondslinkaminoacidstogethertoformproteins.
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25. •AminoAcidTransamination:
•Reaction:Transferofanaminogroupfromoneaminoacidtoaketoacid,forminganewamino
acidandanewketoacid.
•Catalyst:Aminotransferaseenzymes.
•Importance:Involvedinthesynthesisofnon-essentialaminoacidsandinthecatabolismofamino
acids.
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26. 26

27. •Deamination:
•Reaction:Removalofanaminogroupfromanaminoacid,formingammonia(NH3)andaketoacid.
•Catalyst:Deaminaseenzymes.
•Importance:Importantinthebreakdownofaminoacidsforenergyproduction.
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28. •Decarboxylation:
•Reaction:Removalofacarboxylgroupfromanaminoacid,resultinginthereleaseofcarbon
dioxide(CO2)andamines.
•Catalyst:Decarboxylaseenzymes.
•Importance:Canbepartofvariousmetabolicpathways,includingthesynthesisof
neurotransmitters.
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29. Proteins-peptide bond
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30. •Proteinsarelarge,complexmoleculesessentialforthestructure,function,andregulationofcells
andtissuesinlivingorganisms.
•Composedofaminoacidslinkedbypeptidebonds,proteinsexhibitawidevarietyofstructures
andfunctions.
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31. •PrimaryStructure:
•Thelinearsequenceofaminoacidsinapolypeptidechain.
•Example:Theprimarystructureofinsulinisachainof51aminoacids.
•SecondaryStructure:
•Localizedfoldingpatternsresultingfromhydrogenbonding,formingalphahelicesorbetasheets.
•Example:Alphahelicesinkeratin,astructuralproteininhairandnails.
•TertiaryStructure:
•Overallthree-dimensionalshapeofasinglepolypeptidechain,influencedbyinteractionsbetween
aminoacidsidechains.
•Example:Myoglobin,aproteininvolvedinoxygenstorageinmusclecells.
•QuaternaryStructure:
•Arrangementofmultiplepolypeptidechains(subunits)inaproteinwithmorethanonesubunit.
•Example:Hemoglobin,consistingoffoursubunits,eachwithahemegroupforoxygenbinding.
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32. Functions of Proteins:
•Enzymes:
•Example:Catalase,anenzymethatcatalyzesthebreakdownofhydrogenperoxideincells.
•StructuralProteins:
•Example:Collagen,providingstrengthandflexibilitytoconnectivetissues.
•TransportProteins:
•Example:Hemoglobin,transportingoxygeninthebloodstream.
•Hormones:
•Example:Insulin,regulatingbloodglucoselevels.
•Antibodies:
•Example:ImmunoglobulinG(IgG),playingakeyroleintheimmuneresponse.
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33. •Contractile Proteins:
•Example: Actin and myosin, enabling muscle contraction.
•Storage Proteins:
•Example: Ferritin, storing and releasing iron in cells.
•Receptor Proteins:
•Example: Rhodopsin, a light-sensitive receptor protein in the retina.
•Chaperone Proteins:
•Example: Heat shock proteins, assisting in the proper folding of other proteins.
•Cell Adhesion Proteins:
•Example: Integrins, facilitating cell-to-cell and cell-to-matrix interactions.
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34. Protein synthesis
•Proteinsynthesisisacomplexandhighlyregulatedcellularprocessthatinvolvestheproductionof
proteinsfromthegeneticinformationstoredinDNA.
•Itoccursintwomainstages:transcriptionandtranslation.
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35. Transcription
•Initiation:
•RNApolymerasebindstothepromoterregionofageneonDNA.
•DNAunwinds,andtheRNApolymeraseinitiatesthesynthesisofacomplementarymRNAstrand.
•Elongation:
•RNApolymerasemovesalongtheDNAtemplate,synthesizinganmRNAstrandbyadding
complementarynucleotides.
•mRNAissynthesizedinthe5'to3'direction.
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36. •Termination:
•TranscriptionstopswhenRNApolymerasereachesaterminationsignalontheDNA.
•mRNAisreleased,andtheDNAhelixreforms.
•Processing:
•Ineukaryotes,theinitialmRNAtranscript(pre-mRNA)undergoessplicing,wherenon-coding
intronsareremoved,andcodingexonsarejoined.
•A5'capandapoly-AtailareaddedtothemRNA,facilitatingstabilityandtranslation.
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37. 37

38. 38

39. Translation
•Initiation:
•mRNA,smallribosomalsubunit,andinitiatortRNA(carryingmethionine)formacomplex.
•Thecomplexbindstothestartcodon(AUG)onthemRNA.
•Elongation:
•Alargerribosomalsubunitjoinsthecomplex.
•tRNAmoleculesbringaminoacidstotheribosome,guidedbythemRNAcodons.
•Apeptidebondformsbetweenadjacentaminoacids,formingagrowingpolypeptidechain.
•Termination:
•Theribosomereachesastopcodon(UAA,UAG,orUGA)onthemRNA.
•Releasefactorsbindtotheribosome,causingthereleaseofthecompletedpolypeptidechain.
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40. 40

41. 41

42. Key Players in Protein Synthesis:
•mRNA(MessengerRNA):
•CarriesthegeneticcodefromDNAtotheribosomesforproteinsynthesis.
•tRNA(TransferRNA):
•TransfersaminoacidstotheribosomebasedonthemRNAcodons.
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43. •Ribosomes:
•Cellularstructureswhereproteinsynthesisoccurs.
•ComposedofribosomalRNA(rRNA)andproteins.
•AminoAcids:
•Buildingblocksofproteins,broughttotheribosomebytRNA.
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44. 44

45. Regulation of Protein Synthesis:
•TranscriptionalRegulation:
•Controlofgeneexpressionatthetranscriptionallevel.
•RegulatoryproteinsandtranscriptionfactorsinfluencethebindingofRNApolymerasetothe
promoter.
•Post-transcriptionalRegulation:
•InvolvesmodificationstothemRNAtranscriptbeforetranslation.
•AlternativesplicingandmRNAstabilityregulation.
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46. •TranslationalRegulation:
•Controlstherateoftranslation.
•Initiationfactorsandribosome-bindingproteinsinfluencethestartoftranslation.
•Post-translationalModification:
•Alterationstotheproteinaftertranslation.
•Phosphorylation,glycosylation,andadditionofprostheticgroups
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47. Protein Synthesis in Health and Disease
•NormalGrowthandDevelopment:
•Proteinsynthesisisessentialforthegrowth,development,andmaintenanceoftissuesin
organisms.
•GeneticDisorders:
•Mutationsaffectingproteinsinvolvedintranslationcanleadtogeneticdisorders.
•Examplesincludecertaintypesofmusculardystrophyandcysticfibrosis.
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48. •Cancer:
•Dysregulationofproteinsynthesisiscommonincancer.
•Overexpressionormutationsingenesinvolvedinproteinsynthesiscontributetouncontrolledcell
growth.
•NeurologicalDisorders:
•Impairedproteinsynthesisisobservedinneurodegenerativediseases.
•Alzheimer'sandParkinson'sdiseasesareassociatedwithabnormalproteinsynthesisand
aggregation.
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49. Peptide bond
•Apeptidebondisacovalentchemicalbondthatformsbetweentheaminogroup(-NH₂)ofone
aminoacidandthecarboxylgroup(-COOH)ofanotheraminoacid,resultingintheformationofa
peptidelinkage.
•Thesebondsarefundamentalinthecreationofproteinsandpeptides,whichareessential
biologicalmacromolecules.
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50. •CondensationReaction(DehydrationSynthesis):
•Ahydroxylgroupfromthecarboxylendofoneaminoacidreactswithahydrogenatomfromthe
aminogroupofanotheraminoacid.
•Thisresultsinthereleaseofawatermoleculeandtheformationofapeptidebond.
•Theprocessinvolvesthelossofonewatermoleculeforeachpeptidebondformed.
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•H₂N-CH₂-COOH + HO-CH₂-COOH → H₂N-CH₂-CO-NH-CH₂-COOH + H₂O

51. •Peptide Bond Structure:
•Theresultingpeptidebondhasapartialdouble-bondcharacterduetoresonancebetweentwo
possiblestructures.
•The peptide bond is planar, with the carbon and nitrogen atoms involved in the bond lying in the
same plane.
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52. Properties of Peptide Bonds
•Rigidity:
•Thepeptidebondintroducesrigiditytotheproteinbackboneduetothepartialdouble-bond
character.
•RotationaroundtheC-Naxisisrestricted,whichinfluencestheprotein'soverallstructure.
•Directionality:
•Peptidebondshavedirectionality,withanamino(NH)endandacarboxyl(CO)end.
•Proteinsynthesisoccursfromtheaminoterminus(N-terminus)tothecarboxylterminus(C-
terminus).
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53. Peptides and Polypeptides
•Peptides:
•Short chains of amino acids linked by peptide bonds.
•Typically, peptides consist of fewer than 50 amino acids.
•Example:
•The hormone oxytocin is a peptide consisting of nine amino acids.
•Polypeptides:
•Longer chains of amino acids linked by peptide bonds.
•Proteins are often made up of one or more polypeptide chains.
•Example:
•Insulin is a protein consisting of two polypeptide chains linked by disulfide bonds.
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54. •HydrolysisReaction:
•The reverse process of peptide bond formation.
•In the presence of water and specific enzymes (peptidases), a peptide bond can be broken
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H₂N-CH₂-CO-NH-CH₂-COOH + H₂O → H₂N-CH₂-COOH + HO-CH₂-COOH

55. Significance of Peptide Bonds
•ProteinStructure:
•Peptidebondsarecrucialfortheprimarystructureofproteins,formingthelinearsequenceof
aminoacids.
•ProteinFunction:
•Therigidityintroducedbypeptidebondsinfluencestheoverallthree-dimensionalstructureof
proteins,whichisessentialfortheirspecificfunctions.
•BiologicalSignaling:
•Peptidehormonesandneurotransmittersplayessentialrolesincellularsignaling.
•Examplesincludeinsulin(regulatesbloodsugar)andoxytocin(involvedinsocialbonding).
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56. •Enzymes:
•Numerousenzymes,essentialforcatalyzingbiochemicalreactions,consistofpolypeptidechains
linkedbypeptidebonds.
•Insummary,peptidebondsarecriticalintheformationofproteinsandpeptides,providing
structuralintegrityandcontributingtotheirdiversefunctionsinbiologicalsystems.
•Thespecificityofthepeptidebondanditsuniquepropertiesplayafundamentalroleinthe
complexityandfunctionalityofproteinsinlivingorganisms.
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57. Ramachandran's plot, Structural organizations of
proteins (primary, secondary, tertiary)
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58. Ramachandran's plot
•Ramachandran'splotislikeamapthathelpsscientistsunderstandhowthebuildingblocksof
proteins,calledaminoacids,cantwistandturn.
•Ramachandran'splot,namedafteritscreatorGopalasamudramNarayanaRamachandran,isa
graphicalrepresentationoftheenergeticallyallowedregionsofdihedralangles(phiandpsi)for
aminoacidresiduesinproteinstructures.
•Theseanglesdefinetherotationaboutthebondsbetweenthebackboneatomsofadjacentamino
acidresidues.
•Ramachandranplotsareessentialtoolsforanalyzingthestereochemicalqualityofprotein
structures.
•Imagineyou'rebuildingatoywithblocks,andeachblockrepresentsanaminoacid.Thewayyou
connecttheseblocksaffectstheshapeofthetoy.
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59. 59

60. Structural organizations of proteins
•Proteins exhibit a hierarchical structural organization that is essential for their diverse functions in
living organisms.
•The primary, secondary, tertiary, and quaternary structures represent the levels of organization in a
protein.
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61. •Theprimarystructureofaproteinreferstothespecificlinearsequenceofaminoacidsinits
polypeptidechain.
•Thissequenceisencodedbythegenecorrespondingtothatprotein,anditplaysafundamental
roleindeterminingtheprotein'sultimatestructureandfunction.
•AminoAcids:
•Proteinsarecomposedofaminoacidslinkedtogetherinaspecificsequence.
•Thereare20differentaminoacidsthatcanbeincorporatedintoproteins,eachwithauniqueside
chain(R-group).
•PeptideBonds:
•Aminoacidsarelinkedbypeptidebondsduringproteinsynthesis.
•Peptidebondsformbetweentheaminogroup(-NH₂)ofoneaminoacidandthecarboxylgroup(-
COOH)ofanotheraminoacid.
•Theresultingstructureisalinearchainofaminoacids,knownasapolypeptidechain.
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62. •Directionality:
•Theprimarystructureofaproteinhasdirectionality.
•ItisdescribedfromtheN-terminus(aminoterminus)totheC-terminus(carboxylterminus)ofthe
polypeptidechain.
•GeneticCode:
•Thesequenceofaminoacidsisdeterminedbythegeneticcode.
•Eachsetofthreenucleotides(codon)inDNAorRNAcorrespondstoaspecificaminoacidora
stopsignalduringproteinsynthesis.
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63. •Variability:
•Theprimarystructureofproteinscanvarywidelyamongdifferentproteins.
•Evensmallchangesintheaminoacidsequencecanleadtosignificantdifferencesintheprotein's
structureandfunction.
•Post-translationalModifications:
•Insomecases,aminoacidsintheprimarystructureundergopost-translationalmodifications.
•Examplesincludephosphorylation,glycosylation,andacetylation,whichcanimpactprotein
function.
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64. •Thesecondarystructureofproteinsreferstolocalfoldingpatternswithinapolypeptidechain.
•Unlikethelinearsequenceofaminoacidsintheprimarystructure,thesecondarystructure
involvesregular,repetitivearrangementsthatarestabilizedbyhydrogenbondingbetweenamino
acidresidues.
•Thetwomostcommontypesofsecondarystructuresarealphahelicesandbetasheets.
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65. •AlphaHelix:
•Aright-handedhelicalorcoiledstructure.
•Eachturnofthehelixcontainsapproximately3.6aminoacidresidues.
•Thebackboneofthepolypeptidechainformsthehelix,andthesidechainsprojectoutward.
•Stabilizedbyhydrogenbondsformedbetweenthecarbonyloxygenofanaminoacidresidueand
theaminohydrogenoftheaminoacidlocatedfourresiduesaheadinthesequence.
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66. •Alphakeratin,astructuralproteininhair,nails,andtheouterlayeroftheskin,containsalpha
helices.
•Providesstructuralstability.
•Typicallyfoundintheinnerregionsofglobularproteins.
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67. •BetaSheet:
•Formedbyhydrogen-bondedstrandsofthepolypeptidechainrunningalongsideeachother.
•Canbeparallelorantiparallel,dependingonthedirectionoftheadjacentstrands.
•Hydrogenbondsformbetweenthecarbonyloxygenofonestrandandtheaminohydrogenofan
adjacentstrand.
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68. 68

69. •Silkfibroin,theproteininspidersilk,containsantiparallelbetasheets.
•Contributestothestabilityandrigidityofcertainproteinstructures.
•Oftenfoundinthecoreofglobularproteins.
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70. •Turns and Loops:
•Short segments where the polypeptide chain changes direction.
•Connects different secondary structure elements.
•Example:
•Beta turns, which often involve four amino acid residues, are common in proteins.
•Facilitate changes in direction in the protein structure.
•Play a role in connecting different functional domains.
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71. •Coiled-CoilStructures:
•Involvestwoormorealphaheliceswoundaroundeachother.
•Formsasuperhelicalstructure.
•Example:
•Theleucinezippermotif,foundinsometranscriptionfactors,isacoiled-coilstructure.
•Providesstabilityandisinvolvedinprotein-proteininteractions.
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72. •ImportanceofSecondaryStructure:
•FunctionalRoles:
•Thesecondarystructureisoftenlinkedtothebiologicalfunctionofaprotein.
•ProteinFolding:
•Thesecondarystructurecontributestotheoverallfoldingofproteinsintotheirthree-dimensional
shapes.
•StructuralStability:
•Contributestothestabilityandrigidityoftheproteinstructure.
•DiseaseImplications:
•Mutationsaffectingsecondarystructureelementscanleadtodiseases.
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73. •Tertiarystructurereferstothethree-dimensionalarrangementofalltheatomsinasingle
polypeptidechain,includingitssecondarystructureelements,withinaprotein.
•Itrepresentstheoverallfoldingpatternoftheproteinandiscriticalforitsspecificbiological
function.
•Thetertiarystructureisstabilizedbyvariousinteractionsbetweenaminoacidsidechains(R-
groups),includinghydrogenbonds,disulfidebonds,hydrophobicinteractions,ionicbonds,andvan
derWaalsforces.
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74. •FoldingPatterns:
•Thepolypeptidechainfoldsintoaspecificthree-dimensionalshape.
•Thefoldingisdeterminedbytheinteractionsbetweenaminoacidresidues.
•StabilizingInteractions:
•HydrogenBonds:Formedbetweenpolaraminoacidsidechains.
•DisulfideBonds:Covalentbondsbetweencysteineresidues.
•HydrophobicInteractions:Nonpolarsidechainstendtoclustertogethertominimizecontactwith
water.
•IonicBonds:Attractionbetweenpositivelyandnegativelychargedsidechains.
•VanderWaalsForces:Weakattractionsbetweenatomsincloseproximity.
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75. 75

76. •FunctionalDomains:
•Tertiarystructureoftenincludesdistinctregionscalleddomains.
•Domainsarefunctionalandstructuralunitswithinaprotein.
•ActiveSites:
•Theactivesiteofanenzyme,wheresubstratebindingandcatalysisoccur,isafeatureoftertiary
structure.
•Proteinsmayhaveotherfunctionalsites,suchasbindingsitesforligandsorcofactors.
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77. •FlexibilityandDynamics:
•Proteinsarenotstaticstructures;theycanundergoconformationalchanges.
•Tertiarystructurecontributestotheflexibilityanddynamicsofproteins.
•HemeBindinginHemoglobinandMyoglobin:
•Inhemoglobinandmyoglobin,thehemegroupispartofthetertiarystructure.
•Theironioninhemebindstooxygen,facilitatingoxygentransportinblood(hemoglobin)or
oxygenstorageinmuscles(myoglobin).
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78. •DeterminantsofTertiaryStructure:
•AminoAcidSequence:
•Theprimarystructuredictatestheaminoacidcomposition,which,inturn,influencesthetertiary
structure.
•EnvironmentalFactors:
•Thesurroundingenvironment,includingtemperature,pH,andthepresenceofions,caninfluence
tertiarystructurestability.
•ChaperoneProteins:
•Chaperonesassistinthecorrectfoldingofproteins.
•Theypreventmisfoldingandaggregationduringproteinsynthesis.
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79. •ImportanceofTertiaryStructure:
•FunctionalSpecificity:
•Tertiarystructureisintimatelylinkedtothespecificbiologicalfunctionsofproteins.
•MolecularRecognition:
•Tertiarystructurefacilitatestherecognitionandinteractionofproteinswithothermolecules,such
assubstrates,ligands,orotherproteins.
•EnzymaticActivity:
•Enzymesexhibitspecificcatalyticactivitiesbasedontheirtertiarystructure.
•DiseaseImplications:
•Mutationsorstructuralabnormalitiesinthetertiarystructurecanleadtodiseases.
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80. •RibonucleaseA:
•Anenzymewithawell-studiedtertiarystructure.
•Containsseveralalphahelicesandbetasheets.
•ImmunoglobulinG(IgG):
•AnantibodywithaY-shapedtertiarystructure.
•Theantigen-bindingregionispartofthetertiarystructure.
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81. Structural organizations of proteins (quaternary,
Super secondary structures: Domains, Motifs &
Folds)
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82. •Thequaternarystructureofaproteinreferstothespatialarrangementandinteractionsbetween
multipleproteinsubunits,orpolypeptidechains,inacomplex.
•Notallproteinshavequaternarystructure;itischaracteristicofproteinscomposedoftwoormore
polypeptidechains.
•Thequaternarystructureisessentialfortheoverallfunctionandstabilityoftheseproteins.
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83. •Composition:
•Subunits:Proteinswithquaternarystructureconsistofmultiplesubunits.Thesesubunitscanbe
identical(homodimers,homotrimers,etc.)ordifferent(heterodimers,heterotrimers,etc.).
•PolypeptideChains:Eachsubunitisapolypeptidechain,andtheentirecomplexisformedbythe
interactionofthesechains.
•Interactions:
•Non-CovalentBonds:Theinteractionsbetweensubunitsareprimarilynon-covalent.
•Thisincludeshydrogenbonds,vanderWaalsforces,ionicinteractions,andhydrophobic
interactions.
•CovalentBonds:Insomecases,covalentbondsmayalsoplayaroleinstabilizingthequaternary
structure.
•Disulfidebonds,formedbetweencysteineresiduesindifferentchains,areacommonexample.
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84. Intra-molecular and Inter-molecular bonding
•Intramolecularbonding,alsoknownasintramolecularforces,innanoparticlesplaysacrucialrolein
theirstructure,stability,andproperties.
•Theseforcesrefertotheinteractionsthatoccurbetweenatomswithinthesamemoleculeor
nanoparticle.
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85. •RoleinFunction:
•AllostericRegulation:Allostericenzymesoftenhavequaternarystructures.
•Thebindingofamoleculetoonesubunitcaninduceconformationalchangesinothersubunits,
influencingtheenzyme'sactivity.
•Changesinonesubunitcanaffecttheactivityofothersubunitswithinthecomplex.
•Stability:Theinteractionbetweensubunitscontributestotheoverallstabilityoftheprotein.
•Thequaternarystructureprovidesahigherlevelofstabilitycomparedtoindividualpolypeptide
chains.
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86. •ConformationalChanges:Proteinswithquaternarystructuremayundergoconformationalchanges
inresponsetoenvironmentalcuesorbindingevents.
•Thesechangescanaffectthefunctionoftheproteincomplex.
•Understandingthequaternarystructureofproteinsiscrucialforcomprehendingtheirbiological
functions.
•TechniquessuchasX-raycrystallography,nuclearmagneticresonance(NMR)spectroscopy,and
cryo-electronmicroscopyareemployedtostudythethree-dimensionalstructureofprotein
complexesandelucidatetheirquaternaryarrangements.
86

87. Supersecondarystructures
•Supersecondarystructures,alsoknownasmotifsorfolds,areintermediatestructuralelementsthat
aresmallerthantheoveralltertiarystructureofaproteinbutlargerthansecondary
structureslikealphahelicesandbetastrands.
•Theyrepresentrecurringstructuralpatternsorarrangementsofsecondarystructureelementswithin
aprotein.
•Supersecondarystructurescontributetotheoverallthree-dimensionalarchitectureofaproteinand
playacrucialroleindeterminingitsfunction
87

88. •Beta-alpha-betaMotif(β-α-β):
•Thismotifisacommonstructuralfeatureinproteins.
•Ittypicallyconsistsofabetastrandfollowedbyanalphahelixandanotherbetastrand.
•Thebetastrandsareoftenadjacentorantiparalleltoeachother.
•Thismotifisfrequentlyinvolvedinligandbindingorenzymaticactivity.
88

89. •BetaHairpin:
•Abetahairpinisastructuralmotifformedbytwoadjacentantiparallelbetastrandsconnectedbya
reverseturn.
•Itresemblesahairpinshapeandisofteninvolvedinprotein-proteininteractionsandstability.
89

90. •Helix-turn-helixMotif:
•ThismotifiscommoninDNA-bindingproteins.
•Itconsistsoftwoalphahelicesconnectedbyashortturn.
•ThesecondhelixofteninteractswithDNAandisinvolvedinsequence-specificDNArecognition.
90

91. •GreekKeyMotif:
•TheGreekkeymotifisarepeatedpatternoffourantiparallelbetastrandsarrangedinasquareor
rectangularshape.
•Itisacommonstructuralmotifinbetasheetsandisofteninvolvedinformingbetabarrelsorbeta
sheets
91

92. •Beta-meander:
•Abeta-meanderisastructuralmotifinwhichconsecutiveantiparallelbetastrandsareconnected
byturns,formingameanderingorzigzagpattern.
•Thismotifisoftenfoundinbetasheetsandcontributestothestabilityoftheproteinstructure.
92

93. •Four-helixBundle:
•Proteinswithafour-helixbundlesupersecondarystructureconsistoffouralphahelicesarrangedin
abundle.
•Thisarrangementisoftenstableandprovidesastructuralframeworkforvariousfunctions,including
membraneproteinstructures.
93

94. •Coiled-coilMotif:
•Thecoiled-coilmotifisacommonsupersecondarystructureinvolvedin
protein-proteininteractions.
•Itisformedbytwoormorealphaheliceswindingaroundeachother,
creatingacoiledstructure.
•Thismotifisoftenfoundinstructuralandregulatoryproteins.
94

95. •RossmannFold:
•TheRossmannfoldisacommonsupersecondarystructureinenzymesinvolvedinbinding
nucleotides,suchasNAD(P)-bindingproteins.
•Itconsistsofalternatingbetastrandsandalphahelicesarrangedinaspecificpattern.
95

96. •TIMBarrel(TriosephosphateIsomeraseBarrel):
•TheTIMbarrelisasupersecondarystructurefoundinenzymes.
•Itconsistsofeightalphahelicesandeightparallelbetastrands,formingabarrel-likestructure.
•EnzymeswithTIMbarrelstructuresoftencatalyzereactionsinvolvingsmallmolecules
96

97. •Greek Key Barrel:
•SimilartotheGreekKeyMotif,theGreekKeyBarrelisastructuralmotiffoundinproteinswitha
barrel-likeshape.
•ItisformedbythearrangementofantiparallelbetastrandsinawaythatresemblesaGreekkey
pattern
97

98. •Understandingsupersecondarystructuresiscrucialindecipheringtheoverallarchitectureand
functionofproteins.
•Thesestructuralmotifscontributetothediversityofproteinstructuresandtheirabilitytoperforma
widerangeofbiologicalfunctions.
•ExperimentaltechniquessuchasX-raycrystallographyandnuclearmagneticresonance(NMR)
spectroscopyarecommonlyusedtodeterminethethree-dimensionalstructuresofproteinsand
identifysupersecondarystructureswithinthem.
98

99. •Exceptforthesimplestaminoacid,glycine,alloftheotheraminoacidsthatareincorporatedinto
proteinstructuresarechiralinnature.
•Althoughmostaminoacidscanexistinbothleftandrighthandedforms,lifeonEarthismadeof
lefthandedaminoacids,almostexclusively.
•Thereasonbehindthishomochirality(havingthesamehandedness)inbiologicalsystemsisnot
completelyunderstood,anditremainsoneoftheintriguingmysteriesintheoriginsoflife
99

100. •Proteinmisfoldingisaphenomenonwhereaproteinfailstoadoptitsnative,functionalthree-
dimensionalstructure.
•Misfoldedproteinscanhavesevereconsequencesforcellularfunctionandareassociatedwith
variousdiseases.
100

101. •Manyneurodegenerativediseasesarelinkedtoproteinmisfolding.
•Alzheimer'sDisease:Misfoldingofproteinslikebeta-amyloidandtauleadstotheformationof
plaquesandtanglesinthebrain.
•Parkinson'sDisease:Misfoldingofthealpha-synucleinproteincontributestotheformationof
Lewybodiesinbraincells.
•Huntington'sDisease:Expansionofarepeatedsequenceinthehuntingtinproteincauses
misfoldingandaggregationinneurons.
101

102. Structure and functional classification
of proteins; Structure-Function relationship with
protease as an example
BIOCHEMISTRY
BTY 103
102

103. Structural classification of proteins
•FibrousProteins:
•Characteristics:
•ExtendedandStrand-like:Fibrousproteinshavealongandnarrowshape.
•RepetitiveStructure:Oftencharacterizedbyrepetitivesequences.
•Examples:
•Collagen:Providesstrengthandflexibilitytoconnectivetissueslikeskin,tendons,andbones.
•Keratin:Foundinhair,nails,andtheouterlayeroftheskin.
•Fibroin:Constituentofsilkfibers.
103

104. •GlobularProteins:
•Characteristics:
•CompactandSpherical:Globularproteinshaveamorerounded,three-dimensionalstructure.
•DiverseFunctions:Exhibitawiderangeofbiologicalfunctions.
•Examples:
•Enzymes:Catalyzebiochemicalreactions.
•Hemoglobin:Oxygentransportinblood.
•Insulin:Regulatesglucosemetabolism.
•Myoglobin:Oxygenstorageinmuscles.
104

105. •MembraneProteins:
•Characteristics:
•IntegralorPeripheral:Embeddedwithinorassociatedwithcellmembranes.
•TransmembraneRegions:Manyhavehydrophobicregionsthatspanthelipidbilayer.
•Examples:
•IonChannels:Facilitatethepassageofionsacrossmembranes.
•Transporters:Movesubstancesacrossmembranes.
•Receptors:Transmitsignalsfromtheextracellularenvironmenttothecell.
105

106. •DisorderedProteins(IntrinsicallyDisorderedProteins-IDPs):
•Characteristics:
•LackaDefinedStructure:Donotadoptastablethree-dimensionalstructureunderphysiological
conditions.
•ConformationalFlexibility:Exhibitflexibilityanddisorder.
•Examples:
•P53:Involvedincellcycleregulationandapoptosis.
•α-Synuclein:AssociatedwithParkinson'sdisease.
•TauProtein:ImplicatedinAlzheimer'sdisease.
106

107. •Thestructuralclassificationofproteinshighlightsthediversityofproteinarchitectureandfunction.
•Proteinswithsimilarthree-dimensionalstructuresoftensharecommoncharacteristicsand
functions.
•Understandingthestructuralclassesofproteinsisessentialforunravelingtheirrolesinbiological
processesanddesigningtherapeuticinterventionstargetingspecificproteins.
107

108. Functional Classification of Proteins:
•Proteinsservediversefunctionsinlivingorganisms,andtheycanbeclassifiedbasedontheir
biologicalroles.
•Enzymes:
•Function:Catalyzebiochemicalreactionsbyloweringactivationenergy.
•Example:Catalasecatalyzesthedecompositionofhydrogenperoxideintowaterandoxygen.
108

109. •StructuralProteins:
•Function:Providesupportandmaintainthestructureofcellsandtissues.
•Example:Collagenisastructuralproteininconnectivetissues.
•TransportProteins:
•Function:Facilitatethemovementofsubstancesacrossbiologicalmembranesorthroughthe
bloodstream.
•Example:Hemoglobintransportsoxygeninredbloodcells
109

110. •StorageProteins:
•Function:Storeessentialsubstances,suchasaminoacidsormetalions,forlateruse.
•Example:Ferritinstoresironintheliver.
•HormonalProteins:
•Function:Actassignalingmoleculestoregulatephysiologicalprocesses.
•Example:Insulinregulatesglucosemetabolism.
110

111. •Antibodies(Immunoglobulins):
•Function:Playakeyroleintheimmunesystembyrecognizingandneutralizingforeign
substances.
•Example:IgGisanimmunoglobulininvolvedinimmuneresponses.
•ContractileProteins:
•Function:Enablemovementbycontractingandrelaxing.
•Example:Actinandmyosinarecontractileproteinsinmusclecells.
111

112. •ReceptorProteins:
•Function:Bindtospecificmolecules(ligands)toinitiateacellularresponse.
•Example:Gprotein-coupledreceptorsareinvolvedinsignaltransduction.
•RegulatoryProteins:
•Function:Controltheactivityofotherproteinsorcellularprocesses.
•Example:Cyclinsregulatethecellcycle.
•DefensiveProteins:
•Function:Providedefenseagainstpathogens.
•Example:Antimicrobialpeptidesactasadefensemechanismagainstbacteria.
112

113. •Proteinsareincrediblydiverseandversatilemoleculesthatcarryoutawiderangeoffunctions
essentialforlife.
•Theirstructure,fromthelinearsequenceofaminoacidstothecomplexthree-dimensional
arrangements,determinestheirspecificrolesinbiologicalprocesses.
•Thefunctionalclassificationreflectsthediverserolesthatproteinsplayinmaintainingthestructure
andfunctionofcellsandorganisms.
•Understandingproteinstructureandfunctioniscrucialforadvancingourknowledgeofbiologyand
developingtherapeuticinterventions.
113

114. Structure function relationship of proteins
•Thestructure-functionrelationshipofproteinsisafundamentalconceptinmolecularbiologythat
emphasizesthecloseconnectionbetweenthethree-dimensionalstructureofaproteinandits
biologicalfunction.
•Thespecificshapeandpropertiesofaproteindictateitsuniqueroleinthecomplexwebof
biologicalfunctions.
114

115. Structure of Proteases
•ActiveSite:
•CatalyticTriad:Manyproteases,particularlyserineproteases,haveacatalytictriadintheiractive
sitecomposedofserine,histidine,andaspartateresidues.
•CatalyticResidues:Theserineresidueactsasanucleophile,initiatingthecleavageofthepeptide
bond.
•DomainsandMotifs:
•ProteaseDomains:Proteasesoftenhavespecificdomainsresponsibleforsubstraterecognition
andbinding.
•ConservedMotifs:Someproteasesshareconservedsequencemotifs,suchasthecatalytictriadin
serineproteases.
115

116. 116

117. •ZymogenActivation:
•InactiveForm(Zymogen):Manyproteasesareinitiallysynthesizedinaninactiveform,requiring
activation.
•ActivationPeptide:Proteolyticremovalofanactivationpeptideexposestheactivesite,rendering
theenzymecatalyticallyactive.
•Cofactors:
•MetalIons:Someproteasesrequiremetalions(e.g.,zinc)ascofactorsforcatalyticactivity.
•Coenzymes:Certainproteasesmayinteractwithcoenzymestoperformtheirfunctions.
117

118. •Proteasesareclassifiedbasedontheircatalyticmechanismsandactivesiteresidues.
•Herearesomeofthemaintypesofproteases:
•SerineProteases:
•CatalyticResidue:Serine.
•ActiveSiteTriad:Serine,histidine,andaspartate.
•Examples:
•Chymotrypsin,Trypsin,Thrombin,Elastase
•CysteineProteases:
•CatalyticResidue:Cysteine.
•ActiveSiteNucleophile:Cysteinethiolate.
•Examples:
•Papain
•Caspases(involvedinapoptosis)
118

119. •AsparticProteases:
•CatalyticResidue:Asparticacid.
•ActiveSiteAspartateDyad:Twoaspartateresidues.
•Examples:
•Pepsin(foundinthestomach)
•CathepsinD(lysosomalenzyme)
•Metalloproteases:
•CatalyticResidue:Metalion(e.g.,zinc).
•ActiveSiteMetalIon:Coordinateswithspecificaminoacidresidues.
•Examples:
•Matrixmetalloproteinases(MMPs)
•Aminopeptidases
119

120. •ThreonineProteases:
•CatalyticResidue:Threonine.
•ActiveSiteResidue:Partofacatalytictriad.
•Example:
•Proteasomes(involvedinproteindegradation)
•GlutamicProteases:
•CatalyticResidue:Glutamicacid.
•ActiveSiteResidue:Partofacatalyticdyad.
•Example:
•γ-Glutamyltranspeptidase(involvedinglutathionemetabolism)
120

121. •ATP-DependentProteases:
•EnergySource:UseATPhydrolysisforproteolysis.
•Examples:
•Clpproteasefamily,Lonprotease
•SignalPeptidases:
•Function:Involvedincleavingsignalpeptidesfromnewlysynthesizedproteins.
•Examples:
•TypeIandTypeIIsignalpeptidases
•ProteaseComplexes:
•Examples:
•Proteasome:Alargeproteasecomplexinvolvedinthedegradationofubiquitinatedproteins.
•Immunoproteasome:Aspecializedproteasomevariantwithimmune-relatedfunctions.
121

122. Function of Protease
•SubstrateSpecificity:
•CleavageSpecificity:Proteasesexhibitspecificityincleavingpeptidebondsatspecificaminoacid
residues.
•SubstrateRecognition:Thestructureoftheactivesitedeterminestheenzyme'sspecificityfor
certainsubstrates.
122

123. •Catalysis:
•NucleophilicAttack:Thecatalyticresiduesintheactivesitefacilitateanucleophilicattackonthe
carbonylcarbonofthepeptidebond.
•PhysiologicalRoles:
•Digestion:Digestiveproteasesbreakdowndietaryproteinsintopeptidesandaminoacidsfor
absorption.
•CellularRegulation:Proteasesregulatecellularprocesses,includingcellcycleprogressionand
apoptosis.
•BloodClotting:Proteaseslikethrombinplayacrucialroleinthecoagulationcascade.
123

124. 124

125. •ProteaseInhibitors:
•EndogenousInhibitors:Cellsproduceproteaseinhibitorstoregulateproteaseactivity.
•TherapeuticApplications:Proteaseinhibitorsareusedinmedicineforconditionssuchas
HIV/AIDS.
•SignalingPathways:
•ActivationofSignalingMolecules:Proteasescleaveandactivatesignalingmolecules,influencing
cellularresponses.
•ProteolysisasaSignal:Thecleavageofspecificsubstratesactsasasignalinvarioussignaling
pathways.
125

126. Structure-Function Relationship
•Thestructure-functionrelationshipinproteasesisevidentinthefollowingways:
•ActiveSiteSpecificity:Thespecificarrangementofaminoacidresiduesintheactivesite
determinestheprotease'ssubstratespecificityandcatalyticactivity.
•DomainArchitecture:Differentproteaseshavedistinctdomainarchitecturesthatcontributetotheir
uniquefunctionsandsubstraterecognition.
•QuaternaryStructure:Thearrangementofsubunitsinmultimericproteasesinfluencestheir
enzymaticactivityandregulation.
126

127. •CofactorDependency:Proteasesmayrequirespecificcofactorsforoptimalcatalyticactivity,
emphasizingtheimportanceoftheoverallenzymestructure.
•ZymogenActivation:Thepresenceofanactivationpeptideinzymogenshighlightsthestructural
changesnecessaryforproteaseactivation.
•EvolutionaryConservation:Despitevariationsinsequences,conservedmotifsandstructures
highlighttheevolutionaryimportanceofspecificelementsinproteases.
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128. 128