生物大分子結(jié)構(gòu)與功能相互作用力第節(jié)第節(jié)詳解演示文稿第一頁(yè)，共八十二頁(yè)。優(yōu)選生物大分子結(jié)構(gòu)與功能相互作用力第節(jié)第節(jié)第二頁(yè)，共八十二頁(yè)。1,thesecondarystructures2,Supersecondarystructuresanddomains3,Toolstoinvestigatetheproteinconformation4,globularproteinsandSCOP5,fibrousproteins第三頁(yè)，共八十二頁(yè)。ProteinSecondaryStructure■Secondarystructureistheregulararrangementofaminoacidresiduesinasegmentofapolypeptidechain,inwhicheachresidueisspatiallyrelatedtoitsneighborsinthesameway.■Themostcommonsecondarystructuresaretheαhelix,theβ

conformation,andβ

turns.■Thesecondarystructureofapolypeptidesegmentcanbecompletelydefinediftheφand

ψanglesareknownforallaminoacidresiduesinthatsegment.第四頁(yè)，共八十二頁(yè)。10papersfromLinusPaulingandcolleaguespublishedinPNAS,1951第五頁(yè)，共八十二頁(yè)。αhelix310helixπ

helix:theoreticallypossible,butneverfoundintheproteins?sheet:parallelandanti-parallel第六頁(yè)，共八十二頁(yè)。αhelix?sheet3.613helix第七頁(yè)，共八十二頁(yè)。Parametersoffiveactualortheoreticalsecondarystructures:第八頁(yè)，共八十二頁(yè)。αhelix:

thebackboneofthepolypeptidechainisextendedintohelicalstructureWhichIsbuiltupfromonecontinuousregion.αhelix第九頁(yè)，共八十二頁(yè)。φ,ψanglepairapproximately-60°and-50°.Thelengthrangfrom4or5to44residues.Theaveragelengthisaround10residues

第十頁(yè)，共八十二頁(yè)。3.6residuesperturnwithhydrogenbondsbetweenC’=OofresiduesnandNHofresiduesn+4.Theendofαhelicesarepolarandarealmostatthesurfaceofproteinmolecules第十一頁(yè)，共八十二頁(yè)。310helixπ

helix4.416helixN+53residuesperturnanda10atomsbetweenthehydrogenbonddonorandacceptor,N+3第十二頁(yè)，共八十二頁(yè)。Idealizedhelices:第十三頁(yè)，共八十二頁(yè)。Hydrogenbondingpatternsforfourhelices

273103.6134.414第十四頁(yè)，共八十二頁(yè)。第十五頁(yè)，共八十二頁(yè)。Theαhelixhasadipolemoment1.Theoveralleffectisasignificantnetdipolefortheαhelix.Thatgivesapartialpositivechargeattheaminoend

apartialnegativechargeattheCarboxylend(0.5-0.7unitcharge)2.Unitchargeateachendattractligandsofoppositecharge.PhosphategroupsfrequentlybindattheN-terminalofαhelix.Incontrast,positivechargeligandsrarelybindatC-teminal.第十六頁(yè)，共八十二頁(yè)。Someaminoacidsarepreferredinαhelix:Ala(A),Glu(E),Leu(L),andMet(M)

aregoodαhelicesformers.2)

Pro(P),Gly(G),Tyr(Y)andSer(S)

areveryPoorformers3)Themostcommonlocationforanαhelixinaproteinstructureisalongtheoutsideoftheprotein,withonesidefacingthesolutionandtheothersidefacingthehydrophobicinterioroftheprotein.4)αhelicesthatacrossmembranareinaHydrophobicenvironment,mostoftheirsideChainsarehydrophobic第十七頁(yè)，共八十二頁(yè)。第十八頁(yè)，共八十二頁(yè)。第十九頁(yè)，共八十二頁(yè)。Saccharomycescerevisiaemitochondrialthioredoxin3Baoetal.第二十頁(yè)，共八十二頁(yè)。MembraneProteinJ.Deisenhofer,H.MichelScience(245):1463,1989J.Dersenhofer,O.Epp,K.Miki,R.Huber,H.Michel,Nature(318):618,1985J.Deisenhofer,O.Epp,K.Miki,R.Huber,H.Michel,J.Mol.Biol.(180):385,1984H.MichelJ.Mol.Biol.(158):567,1982FirstMembraneProteinStructure:PhotosyntheticReactionCenterofRhodopseudomonasvirdis

紅假單胞菌Complex(foursubunits)solvedin1985(1PRC)NobelChemistryPrizewasawardedtoJ.Deisenhofer,R.Huber,H.Michelin1988.第二十一頁(yè)，共八十二頁(yè)。1)βsheet:

thebackboneofthepolypeptidechainisextendedintoa

zigzagstructure.2)

βsheet

isbuiltupfromacombinationofseveralregionsofthepolypeptidechain.3)Thelengthrangfrom5to10residues.β

sheet第二十二頁(yè)，共八十二頁(yè)。第二十三頁(yè)，共八十二頁(yè)。Theaminoacidecanallruninthesamebiochemicaldirection,amioterminaltocarboxyterminalTheaminoacidcanhavealternatingdirections,theN-terminaltoC-terminalfollowbyC-terminaltoN-terminal第二十四頁(yè)，共八十二頁(yè)。Twoformshaveadistinctivepatternofhydrogen-bondingParallelAntiparallelTheβsheetthatareformedfromseveralβstrandsare

“pleated”第二十五頁(yè)，共八十二頁(yè)。βsheetcanalsocombineintomixedβsheet(About20%ofknownproteinstructuresaremixed)第二十六頁(yè)，共八十二頁(yè)。第二十七頁(yè)，共八十二頁(yè)。Almostalltheβsheethavetwiststrands.This

twisthasthesamehandedness

(right-handed)φ,ψangleswithinthebroadstructurallyallowedregion第二十八頁(yè)，共八十二頁(yè)。第二十九頁(yè)，共八十二頁(yè)。theDouble-headedArrowheadProteaseInhibitorA

Baoetal.第三十頁(yè)，共八十二頁(yè)。第三十一頁(yè)，共八十二頁(yè)。LoopregionfrequentlyparticipateinformingbindingsitesandenzymeactivesitesLoopregionsareatthesurfaceofproteinmoleculesHairpinloops第三十二頁(yè)，共八十二頁(yè)。Hydrogenbondbetweentheoxygenof1stcarboxylgroupandhydrogenofthe4thaminogroupβ-turns:

connecttheendsoftwoadjacentsegmentsofanantiparallelβsheet.第三十三頁(yè)，共八十二頁(yè)。第三十四頁(yè)，共八十二頁(yè)。Productsof13genesinvolvedinpeptidyl-prolylcis-transisomeraseactivitythecommonpresenceofProandGlyresiduesinβturnsβ

turns第三十五頁(yè)，共八十二頁(yè)。

γ

turnHydrogenbondbetweentheoxygenof1stcarboxylgroupandhydrogenofthe3rdaminogroup第三十六頁(yè)，共八十二頁(yè)。ARamachandranplot第三十七頁(yè)，共八十二頁(yè)。第三十八頁(yè)，共八十二頁(yè)。SchematicpicturesofproteinshighlightsecondarystructureSimplifyFacilitateseeingsimilaritybetweenproteinsHelicessometimescylinders第三十九頁(yè)，共八十二頁(yè)。TopologydiagramsareusefulforclassificationofproteinstructuresShowthedirectionofeachβstrandandthewaythestrandsareconnectedtoeachotheralongthepolypeptidechain第四十頁(yè)，共八十二頁(yè)。1,Thesecondarystructures2,Supersecondarystructuresanddomains

3,Toolstoinvestigatetheproteinconformation4,globularproteinsandSCOP5,fibrousproteins第四十一頁(yè)，共八十二頁(yè)。Supersecondarystructures,alsocalledmotifsorsimplyfolds,

areparticularlystablearrangementsofseveralelementsofsecondarystructureandtheconnectionsbetweenthem.第四十二頁(yè)，共八十二頁(yè)。Twoαhelicesthatareconnectedbyashortloopregion.A:helix-turn-helixmotifisspecificforDNAbindingB:thecalciumbindingmotifispresentinmanyproteinsWhosefunctionisregulatedbycalcium.第四十三頁(yè)，共八十二頁(yè)。Thecalcium-bindingmotifissymbolizedbyrighthandExample:thecalciumisboundtothemotifinthetroponin-CThecalcium-bindingmotifissymbolizedbyarighthand.ThismotifiscalledanEFhandbecausethefifthandsixthhelicesfromtheaminoterminusinstructureOfparavalbumin(inmusclerelaxationfoundin1973)whichalabeledEandF,arepartsofthestructurethatwereoriginalusedtoillustratecalciumbindingbythismotif.Theloopregionbetweenthetwoahelicesbindsthecalciumatom.CarboxylsidechainsfromAspandGlu,main-chainC’=OandH2Ofromligandstometalatom.Thehelix-loop-helixmotifprovidesascaffoldThatholdsthecalciumligandinproperpositiontobendandreleasecalcium.c)Thestructureoftroponin-CisbuiltupfromfourEFmotifs.第四十四頁(yè)，共八十二頁(yè)。第四十五頁(yè)，共八十二頁(yè)。Hairpinβmotif(Nospecificfunction)ThestrongpreferenceforβstrandstobeadjacentinβsheetswhentheyareadjacentintheaminoacidSequenceandthustoformahairpinβmotif.Thelengthoftheloopregionbetweentheβstrandsverybutaregenerallyfrom2to5residueslong.Thereisnospecificfunctionassociatedwiththismotif.第四十六頁(yè)，共八十二頁(yè)。Twoexamples:a)bovintrypsininhibitor;b)snakevenomerabutoxin第四十七頁(yè)，共八十二頁(yè)。TheGreekkeymotifExample:theenzymeStaphylococcusnuclease,anenzymethatdegradesDNATheGreekkeymotifisnotassociatedwithanyspecificfunction,Butitoccursfrequentlyinproteinstructures.

第四十八頁(yè)，共八十二頁(yè)。The

β-α-βmotifcontainstwoparallelβstrandsThisloopisofteninvolvedinFormingthefunctionalbindingsite,oractivesite.Theloopregionscanbeofverydifferentlengths,from1or2residuestoover100.ThetwoloopshaveDifferentfunctions.Theloopthatconnectsthecarboxylendoftheβstrandwithaminoendofαhelixisofteninvolvedinformingthefunctionalbindingsite,oractivesite,ofthesestructures.Theseloopregionsthususuallyhaveconservedaminoacidsequencesinhomologousproteins.Incontrast,theotherloophasnotyetfoundtocontributetoanactivesite.第四十九頁(yè)，共八十二頁(yè)。Connectionsbetweenβstrandsinlayeredβsheets第五十頁(yè)，共八十二頁(yè)。Twoarrangementsofβ

strandsstabilizedbythetendencyofthestrandstotwist.Hemolysin(apore-formingtoxinthatkillsacellbycreatingaholeinitsmembrane)fromthebacteriumStaphylococcusaureus(PDB7AHL).photolyase(aproteinthatrepairscertaintypesofDNAdamage)fromE.coli(PDB1DNP).第五十一頁(yè)，共八十二頁(yè)。

氨基酸順序相鄰的花樣通常在三維結(jié)構(gòu)上也靠近

第五十二頁(yè)，共八十二頁(yè)。RNA結(jié)合蛋白(ROP)的四個(gè)

-螺旋折疊為一個(gè)四螺旋束

第五十三頁(yè)，共八十二頁(yè)。

-螺旋的球狀折疊

第五十四頁(yè)，共八十二頁(yè)。

反平行的

-鏈形成桶結(jié)構(gòu)

第五十五頁(yè)，共八十二頁(yè)。上-下--回折桶結(jié)構(gòu)

第五十六頁(yè)，共八十二頁(yè)。

反平行-

結(jié)構(gòu)中的希臘圖案花樣

第五十七頁(yè)，共八十二頁(yè)。果凍卷餅狀桶(jellyrollbarrels)

結(jié)構(gòu)花樣

第五十八頁(yè)，共八十二頁(yè)。

/

TIM桶結(jié)構(gòu)開放扭曲的

/

結(jié)構(gòu)

第五十九頁(yè)，共八十二頁(yè)。開放扭曲的α/β結(jié)構(gòu)中的結(jié)合部位形成裂縫

第六十頁(yè)，共八十二頁(yè)。Proteinmoleculesareorganizedinastructuralhierarchy(等級(jí)）PrimarystructureSecondarystructureTertiarystructure(domains)Quaternarystructure第六十一頁(yè)，共八十二頁(yè)。LargepolypeptidechainsfoldintoseveraldomainsEGF:domainsthatarehomologoustoepidermal(表皮細(xì)胞）growthfactor(53aminoacids)第六十二頁(yè)，共八十二頁(yè)。Constructinglargemotifsfromsmallerones第六十三頁(yè)，共八十二頁(yè)。1,re-visitofthesecondarystructures2,Supersecondarystructuresanddomains3,Toolstoinvestigatetheproteinconformation4,globularproteinsandSCOP5,fibrousproteins第六十四頁(yè)，共八十二頁(yè)。Helpfulwebsites:1,PDB(ProteinDataBank)2,SCOP(StructuralClassificationofProteins)3,comparisonofproteinstructuresin3D第六十五頁(yè)，共八十二頁(yè)。A,X-raycrystallographyB,NMR(nuclearmagneticresonance)C,CD(circulardichroism)D,…第六十六頁(yè)，共八十二頁(yè)。Computerprograms第六十七頁(yè)，共八十二頁(yè)。NMRandNobelPrice:1944:I.I.Rabi,suggeststhatinformationaboutatoms'nucleicanbeobtainedbystudyingtheinternalmagnetismofprotons.Thisformsthefundamentalbasisfortoday'sresonanceimagingtechnologies1952:

PhysicistsE.Purcell(Harvard)andF.Bloch(Stanford)discoverNuclearMagneticResonance(NMR).

1991:R.Ernst,AdvancesinNMRcouldleadtotheabilitytodirectlyobservethechemicalactionofmedicationinthebody.2002:JohnB.Fenn,KoichiTanaka,KurtWüthrichforthedevelopmentofnuclearmagneticresonancespectroscopyfordeterminingthethree-dimensionalstructureofbiologicalmacromoleculesinsolution"第六十八頁(yè)，共八十二頁(yè)。

TheNobelPrizeinChemistry2002"forthedevelopmentofmethodsforidentificationandstructureanalysesofbiologicalmacromolecules""fortheirdevelopmentofsoftdesorptionionisationmethodsformassspectrometricanalysesofbiologicalmacromolecules""forhisdevelopmentofnuclearmagneticresonancespectroscopyfordeterminingthethree-dimensionalstructureofbiologicalmacromoleculesinsolution"

JohnB.Fenn

KoichiTanaka

KurtWüthrich

1/4oftheprize

1/4oftheprize

1/2oftheprizeUSAJapanSwitzerlandVirginiaCommonwealthUniversity

Richmond,VA,USAShimadzuCorp.

Kyoto,JapanEidgen?ssischeTechnischeHochschule(SwissFederalInstituteofTechnology)

Zurich,Switzerland;TheScrippsResearchInstitute

LaJolla,CA,USAb.1917b.1959b.1938第六十九頁(yè)，共八十二頁(yè)。第七十頁(yè)，共八十二頁(yè)。第七十一頁(yè)，共八十二頁(yè)。