生物大分子结构与功能相互作用力详解演示文稿

生物大分子结构与功能相互作用力第节第节详解演示文稿目前一页\总数八十二页\编于二十点优选生物大分子结构与功能相互作用力第节第节目前二页\总数八十二页\编于二十点1,thesecondarystructures2,Supersecondarystructuresanddomains3,Toolstoinvestigatetheproteinconformation4,globularproteinsandSCOP5,fibrousproteins目前三页\总数八十二页\编于二十点ProteinSecondaryStructure■Secondarystructureistheregulararrangementofaminoacidresiduesinasegmentofapolypeptidechain,inwhicheachresidueisspatiallyrelatedtoitsneighborsinthesameway.■Themostcommonsecondarystructuresaretheαhelix,theβ

conformation,andβ

turns.■Thesecondarystructureofapolypeptidesegmentcanbecompletelydefinediftheφand

ψanglesareknownforallaminoacidresiduesinthatsegment.目前四页\总数八十二页\编于二十点10papersfromLinusPaulingandcolleaguespublishedinPNAS,1951目前五页\总数八十二页\编于二十点αhelix310helixπ

helix:theoreticallypossible,butneverfoundintheproteinsßsheet:parallelandanti-parallel目前六页\总数八十二页\编于二十点αhelixßsheet3.613helix目前七页\总数八十二页\编于二十点Parametersoffiveactualortheoreticalsecondarystructures:目前八页\总数八十二页\编于二十点αhelix:

thebackboneofthepolypeptidechainisextendedintohelicalstructureWhichIsbuiltupfromonecontinuousregion.αhelix目前九页\总数八十二页\编于二十点φ,ψanglepairapproximately-60°and-50°.Thelengthrangfrom4or5to44residues.Theaveragelengthisaround10residues

目前十页\总数八十二页\编于二十点3.6residuesperturnwithhydrogenbondsbetweenC’=OofresiduesnandNHofresiduesn+4.Theendofαhelicesarepolarandarealmostatthesurfaceofproteinmolecules目前十一页\总数八十二页\编于二十点310helixπ

helix4.416helixN+53residuesperturnanda10atomsbetweenthehydrogenbonddonorandacceptor,N+3目前十二页\总数八十二页\编于二十点Idealizedhelices:目前十三页\总数八十二页\编于二十点Hydrogenbondingpatternsforfourhelices

273103.6134.414目前十四页\总数八十二页\编于二十点目前十五页\总数八十二页\编于二十点Theαhelixhasadipolemoment1.Theoveralleffectisasignificantnetdipolefortheαhelix.Thatgivesapartialpositivechargeattheaminoend

apartialnegativechargeattheCarboxylend(0.5-0.7unitcharge)2.Unitchargeateachendattractligandsofoppositecharge.PhosphategroupsfrequentlybindattheN-terminalofαhelix.Incontrast,positivechargeligandsrarelybindatC-teminal.目前十六页\总数八十二页\编于二十点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目前十七页\总数八十二页\编于二十点目前十八页\总数八十二页\编于二十点目前十九页\总数八十二页\编于二十点Saccharomycescerevisiaemitochondrialthioredoxin3Baoetal.目前二十页\总数八十二页\编于二十点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

红假单胞菌Complex(foursubunits)solvedin1985(1PRC)NobelChemistryPrizewasawardedtoJ.Deisenhofer,R.Huber,H.Michelin1988.目前二十一页\总数八十二页\编于二十点1)βsheet:

thebackboneofthepolypeptidechainisextendedintoa

zigzagstructure.2)

βsheet

isbuiltupfromacombinationofseveralregionsofthepolypeptidechain.3)Thelengthrangfrom5to10residues.β

sheet目前二十二页\总数八十二页\编于二十点目前二十三页\总数八十二页\编于二十点Theaminoacidecanallruninthesamebiochemicaldirection,amioterminaltocarboxyterminalTheaminoacidcanhavealternatingdirections,theN-terminaltoC-terminalfollowbyC-terminaltoN-terminal目前二十四页\总数八十二页\编于二十点Twoformshaveadistinctivepatternofhydrogen-bondingParallelAntiparallelTheβsheetthatareformedfromseveralβstrandsare

“pleated”目前二十五页\总数八十二页\编于二十点βsheetcanalsocombineintomixedβsheet(About20%ofknownproteinstructuresaremixed)目前二十六页\总数八十二页\编于二十点目前二十七页\总数八十二页\编于二十点Almostalltheβsheethavetwiststrands.This

twisthasthesamehandedness

(right-handed)φ,ψangleswithinthebroadstructurallyallowedregion目前二十八页\总数八十二页\编于二十点目前二十九页\总数八十二页\编于二十点theDouble-headedArrowheadProteaseInhibitorA

Baoetal.目前三十页\总数八十二页\编于二十点目前三十一页\总数八十二页\编于二十点LoopregionfrequentlyparticipateinformingbindingsitesandenzymeactivesitesLoopregionsareatthesurfaceofproteinmoleculesHairpinloops目前三十二页\总数八十二页\编于二十点Hydrogenbondbetweentheoxygenof1stcarboxylgroupandhydrogenofthe4thaminogroupβ-turns:

connecttheendsoftwoadjacentsegmentsofanantiparallelβsheet.目前三十三页\总数八十二页\编于二十点目前三十四页\总数八十二页\编于二十点Productsof13genesinvolvedinpeptidyl-prolylcis-transisomeraseactivitythecommonpresenceofProandGlyresiduesinβturnsβ

turns目前三十五页\总数八十二页\编于二十点

γ

turnHydrogenbondbetweentheoxygenof1stcarboxylgroupandhydrogenofthe3rdaminogroup目前三十六页\总数八十二页\编于二十点ARamachandranplot目前三十七页\总数八十二页\编于二十点目前三十八页\总数八十二页\编于二十点SchematicpicturesofproteinshighlightsecondarystructureSimplifyFacilitateseeingsimilaritybetweenproteinsHelicessometimescylinders目前三十九页\总数八十二页\编于二十点TopologydiagramsareusefulforclassificationofproteinstructuresShowthedirectionofeachβstrandandthewaythestrandsareconnectedtoeachotheralongthepolypeptidechain目前四十页\总数八十二页\编于二十点1,Thesecondarystructures2,Supersecondarystructuresanddomains

3,Toolstoinvestigatetheproteinconformation4,globularproteinsandSCOP5,fibrousproteins目前四十一页\总数八十二页\编于二十点Supersecondarystructures,alsocalledmotifsorsimplyfolds,

areparticularlystablearrangementsofseveralelementsofsecondarystructureandtheconnectionsbetweenthem.目前四十二页\总数八十二页\编于二十点Twoαhelicesthatareconnectedbyashortloopregion.A:helix-turn-helixmotifisspecificforDNAbindingB:thecalciumbindingmotifispresentinmanyproteinsWhosefunctionisregulatedbycalcium.目前四十三页\总数八十二页\编于二十点Thecalcium-bindingmotifissymbolizedbyrighthandExample:thecalciumisboundtothemotifinthetroponin-CThecalcium-bindingmotifissymbolizedbyarighthand.ThismotifiscalledanEFhandbecausethefifthandsixthhelicesfromtheaminoterminusinstructureOfparavalbumin(inmusclerelaxationfoundin1973)whichalabeledEandF,arepartsofthestructurethatwereoriginalusedtoillustratecalciumbindingbythismotif.Theloopregionbetweenthetwoahelicesbindsthecalciumatom.CarboxylsidechainsfromAspandGlu,main-chainC’=OandH2Ofromligandstometalatom.Thehelix-loop-helixmotifprovidesascaffoldThatholdsthecalciumligandinproperpositiontobendandreleasecalcium.c)Thestructureoftroponin-CisbuiltupfromfourEFmotifs.目前四十四页\总数八十二页\编于二十点目前四十五页\总数八十二页\编于二十点Hairpinβmotif(Nospecificfunction)ThestrongpreferenceforβstrandstobeadjacentinβsheetswhentheyareadjacentintheaminoacidSequenceandthustoformahairpinβmotif.Thelengthoftheloopregionbetweentheβstrandsverybutaregenerallyfrom2to5residueslong.Thereisnospecificfunctionassociatedwiththismotif.目前四十六页\总数八十二页\编于二十点Twoexamples:a)bovintrypsininhibitor;b)snakevenomerabutoxin目前四十七页\总数八十二页\编于二十点TheGreekkeymotifExample:theenzymeStaphylococcusnuclease,anenzymethatdegradesDNATheGreekkeymotifisnotassociatedwithanyspecificfunction,Butitoccursfrequentlyinproteinstructures.

目前四十八页\总数八十二页\编于二十点The

β-α-βmotifcontainstwoparallelβstrandsThisloopisofteninvolvedinFormingthefunctionalbindingsite,oractivesite.Theloopregionscanbeofverydifferentlengths,from1or2residuestoover100.ThetwoloopshaveDifferentfunctions.Theloopthatconnectsthecarboxylendoftheβstrandwithaminoendofαhelixisofteninvolvedinformingthefunctionalbindingsite,oractivesite,ofthesestructures.Theseloopregionsthususuallyhaveconservedaminoacidsequencesinhomologousproteins.Incontrast,theotherloophasnotyetfoundtocontributetoanactivesite.目前四十九页\总数八十二页\编于二十点Connectionsbetweenβstrandsinlayeredβsheets目前五十页\总数八十二页\编于二十点Twoarrangementsofβ

strandsstabilizedbythetendencyofthestrandstotwist.Hemolysin(apore-formingtoxinthatkillsacellbycreatingaholeinitsmembrane)fromthebacteriumStaphylococcusaureus(PDB7AHL).photolyase(aproteinthatrepairscertaintypesofDNAdamage)fromE.coli(PDB1DNP).目前五十一页\总数八十二页\编于二十点

氨基酸顺序相邻的花样通常在三维结构上也靠近

目前五十二页\总数八十二页\编于二十点RNA结合蛋白(ROP)的四个-螺旋折叠为一个四螺旋束

目前五十三页\总数八十二页\编于二十点

-螺旋的球状折叠

目前五十四页\总数八十二页\编于二十点

反平行的-链形成桶结构

目前五十五页\总数八十二页\编于二十点上-下--回折桶结构

目前五十六页\总数八十二页\编于二十点

反平行-结构中的希腊图案花样

目前五十七页\总数八十二页\编于二十点果冻卷饼状桶(jellyrollbarrels)

结构花样

目前五十八页\总数八十二页\编于二十点

/

TIM桶结构开放扭曲的/结构

目前五十九页\总数八十二页\编于二十点开放扭曲的α/β结构中的结合部位形成裂缝

目前六十页\总数八十二页\编于二十点Proteinmoleculesareorganizedinastructuralhierarchy(等级）PrimarystructureSecondarystructureTertiarystructure(domains)Quaternarystructure目前六十一页\总数八十二页\编于二十点LargepolypeptidechainsfoldintoseveraldomainsEGF:domainsthatarehomologoustoepidermal(表皮细胞）growthfactor(53aminoacids)目前六十二页\总数八十二页\编于二十点Constructinglargemotifsfromsmallerones目前六十三页\总数八十二页\编于二十点1,re-visitofthesecondarystructures2,Supersecondarystructuresanddomains3,Toolstoinvestigatetheproteinconformation4,globularproteinsandSCOP5,fibrousproteins目前六十四页\总数八十二页\编于二十点Helpfulwebsites:1,PDB(ProteinDataBank)2,SCOP(StructuralClassificationofProteins)3,comparisonofproteinstructuresin3D目前六十五页\总数八十二页\编于二十点A,X-raycrystallographyB,NMR(nuclearmagneticresonance)C,CD(circulardichroism)D,…目前六十六页\总数八十二页\编于二十点Computerprograms目前六十七页\总数八十二页\编于二十点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"目前六十八页\总数八十二页\编于二十点

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

JohnB.Fenn

KoichiTanaka

KurtWüthrich

1/4oftheprize

1/4oftheprize

1/2oftheprizeUSAJapanSwitzerlandVirginiaCommonwealthUniversity

Richmond,VA,USAShimadzuCorp.

Kyoto,JapanEidgenössischeTechnischeHochschule(SwissFederalInstituteofTechnology)

Zurich,Switzerland;TheScrippsResearchInstitute

LaJolla,CA,USAb.1917b.1959b.1938目前六十九页\总数八十二页\编于二十点目前七十页\总数八十二页\编于二十点目前七十一页\总数八十二页\编于二十点3Dstructurecomparison:

目前七十二页\总数八十二页\编于二十点1,re