1 1氨基酸selenocysteine硒代胱氨酸

Part ProteinstructureandChapter1TheCovalentStructureofAminoIThecompositionofnatureNaturalproteinsarebuiltalmostexclusivelyfromthesetof18commonproteinL-aminoacids,theL-iminoacidproline,andglycine.ArareexceptionistheincorporationofL-selenocysteine(硒代胱氨酸)intoafewproteins.IISTRUCTUREOFTHEAMINOEachaminoacid(exceptforproline)has:acarboxylgroup,anaminoadistinctivesidechain("R-group")bondedtotheα-carbonatomlnproteins,almostallofthesecarboxylandaminogroupsarecombinedinpeptidelinkageand,ingeneral,arenotavailableforchemicalreactionexceptforhydrogenbondformation.(FigureItisthenatureofthesidechainsthatultimatelydictatestheroleanaminoacidplaysinaprotein.Thesidechains(R)oftheaminoacidresiduesprovidethevarietyoffunctionalgroupsthatconferparticularpropertiesonindividualproteinmolecules,leadingtoaspecificfoldeddegreeofstateofabilitytoformcomplexeswithligandsorothermacromolecules,enzymeactivity,etc.beingevolutionhasselectedonlypartofasetof sequences(outofaverymuchlargernumber[20n,wherenisthenumberofaminoacidresidues]ofpotentialsequences)thatcanformfunctionallyusefulproteinmolecules.Naturealsofindstwenty(twentyoneifselenocysteineincluded)mRNA-encodedandribosomallyincorporatedaminoacidsinadequateforthediversefunctionsrequiredofproteins,andmanycovalentmodificationsofnascentpolypeptidechainstakeplaceduringthebiosynthesisandmaturationofproteinmolecules.ToclassifytheaminoacidsaccordingtothepropertiesoftheirsidechainsAminoacidswithnonpolarsideAminoacidswithunchargedpolarsideAminoacidswithacidicsideAminoacidswithbasicside AminoacidswithnonpolarsideEachoftheseaminoacidshasanonpolarsidechainthatdoesbindorgiveoffprotonsorparticipateinhydrogenorionicbonds.Thesidechainsoftheseaminoacidscanbethoughtas"oily"or”lipid-like,apropertythatpromoteshydrophobicinteractions.Locationofnopolaraminoacidsinproteins:lnproteinsfoundaqueoussolutions,thesidechainsofthenonpolaraminoacidstendtoclustertogetherintheinterioroftheproteinlnproteinsthatarelocatedinahydrophobicenvironment,suchasamembraneStructure:Thesimplestaminoacid,uniqueamongtheproteinaminoacidsinitslackofdissymmetry.Glycinefrequentlyplaysanimportantroleinproteinstructureswherethelackofa-carbonatompermitsasubstantiallygreaterdegreeofconformationalflexibilityandattainableconformationalspacethanforanyotherresidue.Functionandpositions:1.Glycineisthusoftenlocatedintightturns,andinpositionswherebulkysidechainswouldstericallypreventclosepackingofhelices(asincollagen)orbindingofTheabsenceofastericallyhinderingsidechain-----Glycinealsoconfersgreaterthannormalchemicalreactivityatadjacentpeptidebonds.Forexample,Asn-Glysequencescanformcyclicimidestructures,withdeamidation,muchmorereadilythanotherAsn-Xaasequences.Glycinealsocontributestositesrecognizedbyenzymescatalyzingspecificmodificationsofproteins,suchasthesignalsequencesforN-terminalmyristoylation(十四酰基化，CH2(CH2)12CO－)andargininemethylation.Structure:Alanine是20种氨基酸中最 Oneofthemostabundantaminoacidresiduesinproteins,alanineisweaklyhydrophobic.ChemicalreactivityisveryFeature:Moderatelyresiduealiphaticside reducesconformational conferssterichindrancetochemicalreactionsattheadjacentpeptidebonds.Feature:Hydrophobicresiduealiphaticsidechain. the-branchedsidechainstericallyhinderereactionsatadjacentpeptideThehydrophobicsidechainprefersalocationwithintheinterioroffoldedProteinstructures,andthe-sheetsecondarystructurealsoaccommodatesthesidechainmorereadilythandoesan-helix.Isoleucinehasasecondasymmetric AlargehydrophobicOftenthemostcommonindividualaminoacidinglobularproteins,itsuppliesalargeproportionofthealiphaticsidechainsthatconstitutethehydrophobiccorescharacteristicofthisclassofprotein.Amajorcomponentoftransmembranehelicesinintegralmembraneproteins.Distributedinaregularpattern``leucinezipper''Structure:Thebulkyhydrophobicchainofphenylalaninewithphenyl Someweaklypolarpropertiesthatcontributetopreferredorientationsininteractionswithotheraromaticringsandotherpolar. Animportantconstituentofhydrophobiccoresofglobularproteinsandtransmembranedomainsofintegralmembraneproteins.Structure:Oneofthetwosulfur-containingproteinamino（thioether Similarinitsbulkandhydrophobicitytoleucine. Thesulfuratomcaninteractwithmetalions, andischemicallyreactive,particularlytowardoxidizingThethioethergroupcanalsobealkylatedandreactswithcyanogenbromideunderacidicconditionsStructure:AminoacidwithindoleNHTryptophanresiduesfrequentlyplayakeyroleinstructuralpackinginteractions.ThehighhydrophobicityofthesidechainistemperedbythepresenceoftheindoleNHgroup.Tryptophanresiduesoftenformpartofligand-bindingsites.Theindoleringoftryptophanresiduesissusceptibletoelectrophilicattack.ThelightsensitivityofproteinsistoalargeextentduetotheoxidativedegradationoftryptophanTryptophanresidueshavethegreatestUVabsorbanceandfluorescenceoftheproteinaminoStructure:asecondaryaminoacidwith prolineresidueshaverestrictedconformationalmobility.prolineresiduesareoftenlocatedatthesurfacesofproteinsintightturns. unabletotakepartinfullα-helicalhydrogenbonding, theyconferadistortiononthehelicalaxis.Thepresenceofcispeptidylprolinebondsinproteins(aswellasthemorefrequenttrans1).prolineresiduesareunreactive.2). specificendopeptidasesoccurproline-dependentpropertiesofpeptidesandproteinsAminoacidswithunchargedpolarsideTheseaminoacidshavezeronetchargeatneutral AminoacidwiththeprimaryaliphatichydroxylgroupBothadonorandacceptorofhydrogenbonds.frequentlyinteractingwithsolventwateratthesurfaceoffoldedproteins.However,itsnucleophilicityisenormouslyenhancedintheactivesitesofimportantclassesofproteases(theserineproteases)andMorestablecovalentlinksarealsoformedinThoseformedwithcarbohydrate(O-linkedglycosylation)andphosphateareimportantStructureand Sharessomechemicalandbiochemicalpropertieswithserineresidues,providingsitesforO-linkedglycosylationandphosphorylation,butisrelativelystericallyhinderedandchemicallylessreactive. Thepossessionofasecondchiralcenter.Structure:AminoacidwiththiolThethiolgroupofcysteine,initsdeprotonatedform,thiolate,isapowerfulnucleophile,readilyreactingwithaldehydesandacylatingandalkylatingreagents.Itsaffinityformetalionssuchaszine,iron,andcopper(andtoxicmetalssuchascadmiumandmercury)Theformationofdisulfidecross-linkswithinorbetweenpeptidechainsthroughoxidationofcysteinetocystineresiduesprovidesessentialstabilitytomanyextracellularproteins.cysteineresiduesmayalsobemodifiedbyCysteineresiduescanalsoserveforcovalentlinkageofprostheticgroupssuchasheme.Cysteineresiduesundergo-eliminationalkalineThe-amidegroupofasparagineisahydrogenbonddonorandacceptor.Asparagineresiduesareoftenlocatedinturnsinproteinfoldedstructures.TheamidegroupisrelativelyeasilyIntheabsenceofsterichindrance,acyclicimidestructuremayform(withlossof1).thismayundergoracemizationandsubsequentcleavagetoformL-orD-aspartylorL-orD-isoaspartylresidues.2).Theimidestructureisalsosusceptibletoreactionwithhydroxylamine,resultingincleavageofthepeptidechain.AmajorroleofasparagineisasthelinkagesiteforN-Iinkedglycosylation,mainlyinextracellularorextramembranoussegmentsofeukaryoticglycoproteins.Anecessary,butnotsufficient,conditionforthetransferoftheglycosylmoietytoasparagineisthesequence-Asn-Xaa-(SerorThr)Thepropertiesofglutamineareingeneralsimilartothoseofasparagine,although,astheamideofanacidweakerthanasparticacid,glutamineresiduesarelesslabilethanasparagineresidues.Structure:AminoacidwithphenolichydroxylConfersasignificantdegreeofpolarity,andthesidechainisgenerallypartiallyexposedtosolventinglobularproteinstructures.Mosttyrosineresiduesareneutralatphysiological Actasligandsformetals,suchasFe2+,andtakepartinhydrogenbondingasdonorandacceptor.Thephenolateisareactivenucleophile,bothatthe andaromaticringcarbonCovalentinvivomodificationsincludephosphorylation,sulfation,and,ininvertebrateextracellularproteins,cross-linkingtoothertyrosineTyrosineresiduesarealsothesourceofthyroidAminoacidswithacidicsideTheaminoacidsasparticandglutamicacidareprotondonors.TheseaminoacidsarenegativelychargedatphysiologicpHAsparaticStructure:AspartylresiduewithtwocarboxylicacidThecarboxylicacidgroupsofaspartylresidues(pKatypicallyabout aregenerallyionizedascarboxylatesunderphysiological Thehighlypolarsidechainsarepredominantlylocatedonthesurfacesofproteins,wheretheymaycontributetometalionbindingsites,inparticularforCa2+,andsitesforpositivelycharged Stronghydrogenbondsarealsoformedbetweenthecarboxylategroupanddonorgroupssuchasguanidinium Theaspartyl-carboxylgroupmayalsotakepartdirectlyinenzymiccatalysis.suchaspepsin,reninandretroviralproteases.Theaspartyl-carboxylgroupformsanintermediateacylphosphateduringcatalysisbythecation-translocatingNa+,K+-ATPaseandCa2+-ATPaseofplasmamembranesandCa2+-ATPaseofsarcoplasmicreticulum.Asparticacidsidechainsundergotypicalreactionsofcarboxylic2)Theproximityoftheside-chaincarboxylgrouptothea-carboxylpeptidebondpermitssignificantneighboringgroupeffectsindiluteacidconditionsaspartylpeptidebondsaremorerapidlyhydrolyzedthanotheraminoacylpeptidebonds.(Asp-Pro)4).Asparticacidresiduesmayalsobemodifiedinvivoto-hydroxyasparticacidresidues.GlumaticThecarboxylgroupofglutamicacidresidueshasahigherintrinsicpKa(around4.5)thanthatofasparticacidresidues,butingeneralhassimilarfunctionsandpropertiesincontributingtoelectrostaticandhydrogenbondinginteractionswithinproteinsandwithligands,includingmetalions.Glutamicacidresiduesdonot.however,possessunusualpeptidebondlability,noraretheyessentialactive-siteresiduesinacidInvivomodificationto-carboxyglutamicacidresiduesisessentialtothefunctionofvariousblood-clottingproteins,suchasprothrombin,wherethemalonicacidgroupenhancesaffinityforCa2+.D.AminoacidswithbasicsideThesidechainsofthebasicaminoacidsacceptAtphysiologicpHthesidechainsoflysineandargininearefullyionizedandpositivelycharged.lncontrast,histidineisweaklybasic.Structure:AminoacidwithguanidineFeature:Thestronglybasic(pKaaround12.0)guanidinegroupofarginineresiduesisprotonatedatallphysiologicallyrelevantPHsurfacelocalizationofargininesidechainsArginineresiduesfunctioninproteinsgenerallyaspositivelychargedgroups,contributingtothebindingofnegativelychargedligands.Togetherwithlysineresidues,arginineresiduesprovidepositivelychargedsignalsformembraneproteinassembly,pro-proteincleavage,andnuclearandnucleolarlocalization.RatherunreactivechemicallyatneutralPH;atalkalinePH.arginineresiduesyieldcyclic,frequentlyfluorescent,productswith-or-diketonesandrelatedcompounds.InvivomethylalionandADP-ribosylationareimportantmodificationsAtneutralitymostlysylsidechainbearapositivechargeandaregenerallyexcludedfromthepolarinteriorsofglobularproteins.Thealiphatictetramethylenegroupishydrophobic,butthehydrophilicityoftheprotonatedaminogroupdominates.Thelongflexiblesidechaincontributestoalackofdefinitionofmany-aminogroupsincrystallographicallydeterminedstructures.Ascarriersofpositivecharge,lysineresiduescontributetothebindingofnegativelychargedligands,ofteninvolvingstronghydrogenbonds.Chemically,thereactionsoflysinesidechainsarethosetypicalofprimaryaliphaticamines Invivo,lysineisthelinkagepointformanyprostheticgroups,suchasbiotinandretina视网膜醛.Thesidechainisalsothesiteofenzyme-catalyzedoxidation,yieldingavarietyofcross-linkingstructuresincollagenandelastinandhydroxylationtohydroxylysineresidues.Structure:AminoacidwithimidazoleTheimidazolegroupofhistidineresidueshasatypicalPKaround6.5,closertoneutralitythanotherfunctionalgroupsonproteins.Histidineresiduesfrequentlyactasproton-transferringcatalystsinenzymeHistidinesidechainsarealsofavoredligands,togetherwithcysteine,forbindingmetalionssuchasZn2+,Cu2+,andFe2+.theimidazolegroupisanucleophilcthatisacylatedbycarboxylicacidanhydrides(althoughtheproductsarehydrolyt