中山大学生物化学课件.ppt

中山大学生物化学课件.ppt

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4ProteinFunction4.1Generalfeatures4.2Oxygen-bindingproteins4.3Immunoglobulins4.4Musclecontractionliguofu4.1Generalfeatures1.Versatileinfunction2.Beinghardtostudy3.FunctionviainteractionTheinteractionwithothermolecule（ligand）isreversible.Theinterfacebetweenthebindingsiteiscomplementaryinstructure,makingsuchinteractionhighlyspecific.Structuredynamicnessofaproteinisusuallyessentialforsuchinteractions.liguofu4.1Generalfeatures4.2Oxygen-bindingproteins4.3Immunoglobulins4.4Musclecontraction4ProteinFunctionliguofuQuantitativedescriptionofinteraction

（1）Protein+nLigandPLnliguofuQuantitativedescriptionofinteraction

（2）IfkdisconstantliguofuQuantitativedescriptionofinteraction（3）IfkdisnotconstantKdliguofuQuantitativedescriptionofinteraction（4）liguofuQuantitativedescriptionofinteraction（5）liguofuTheiron-porphyrininhemoglobinaccountsfortheredcolorofblood,thecopper-porphyrininhemocyaninforbluecolorofblood,andthemagnesium-porphyrininchlorophyllisresponsibleforthegreenofplants.liguofuStructureofPorphyrinPyrroleringMethenebridgeliguofuOxygencanbeboundtoaheme

（1）Heme=ProtoporphyrinIX+Fe2+NoneoftheaasidechainsinproteinsissuitedforreversiblebindingO2HemeprostheticgroupTransitionmetals,Fe&Cu,haveastrongtendencytobindO2needmorecommonlyliguofuOxygencanbeboundtoaheme

（2）Heme=ProtoporphyrinIX+Fe2+lFreeIronpromotestheformationofhighlyreactiveoxygenspeciessuchashydroxylradicals.lCoordinatedNatomshelppreventtheconversionofFe2+toFe3+liguofuMbhasasinglebindingsiteforoxygenMyoglobin:

153residues,16700DaHis93/F8His64/E7liguofuOxygencanbeboundtoaheme（3）lInfreehememolecules,reactionofoxygenatoneofthetwo“open”coordinationbondsofironcanresultinirreversibleconversionofFe2+toFe3+lInheme-containingproteins,thisreactionispreventedbysequesteringthehemedeepwithinaproteinstructurewhereacesstothetwo“open”coordinationbondsisrestricted.Oneofthesetwocoordinationbondsisoccupiedbyaside-chainNofaHisresidue.NOCOAlsoliguofuQuantitativedescriptionofMbbindingO2liguofuProteinstructureaffectsligandsbind

（1）InfreehemeorInmyoglobinInfreehemeInmyoglobinhemeorliguofu“Breathing”:

MolecularmotionsThebindingofO2tohemeinmyoglobindependsonits“breathing”InmyoglobinProteinstructureaffectsligandsbind

（2）liguofuHbisthemost-studiedandbest-understoodprotein1.Hemoglobinwasthefirstproteintobecrystallized（in1849）;thefirsttobeassociatedwithaspecificphysiologicalfunction（around1875）;oneofthefirstproteinstohaveitsmolecularweightdeterminedcorrectly（64,500）;thefirsteukaryoticmessenger（mRNA）tobeisolatedandsubsequentlysequenced.thefirsteukaryoticproteintobesynthesizedinacell-freesysteminvitro;thesecondproteinhavingits3-Dstructuredetermined（1969）.liguofu2.The“redcoloringmatter”（hemoglobin）ofanimalbloodcouldbebroughttocrystallization,withcrystalformscharacteristicoftheirbiologicalorigins（1840s-1860s）.3.Reversibleinterconversionofoxyhemoglobinanddeoxyhemoglobinwasrevealedbyusingspectroscope（1860s）.4.Treatmentofhemoglobinwithacidgaveacolorlessalbuminoidconstituent（globin）andarediron-containingmaterial（by1870）.5.Thestructureofhemewaselucidatedtobeatetrapyrrol（porphyrin）derivativebychemicalsynthesis（HansFischer,1929）.6.Similartetrapyrrolderivativesarealsousedasprostheticgroupsofotherproteins（e.g.,thecytochromesthatfunctioninbiologicaloxidationandphotosynthesis!

liguofuHbhasfoursubunitsMr=64,500141residues146residuesliguofuHbsubunitsarestructurallysimilartomyoglobinsubunitlackstheshortDhelixDhelixliguofuconservedinallknownglobinsconserved27positionsareidentical,18%82143liguofu30residuesInteractionsinthefoursubunits19residues19residuesHydrophobicinteractionsHbondsSaltbondsliguofuThisiscalledTensestate（deoxyHb）SomeionpairsarenotshownhereIonpairsatthe1/2and2/1interface

（1）liguofuIonpairsatthe1/2and2/1interface

（2）IonpairsstabilizetheTstateofdeoxyHbliguofuQuantitativedescriptionofHbbindingO2

（1）liguofuHillplotnH:

hillcoefficientQuantitativedescriptionofHbbindingO2（3）liguofuHbundergoesastructuralchangeonbindingO2

（1）TensestateismorestableandthusthepredominantconformationofdeoxyHbRelaxedstateisthepredominantconformationofhigheraffinitytoO2BindingO2ValE11liguofuIntheTstate,theporphyrinisslightlypuckered,causingthehemeirontoprotrudesomewhatontheproximalHis（HisF8）side.ThebindingofO2causesthehemetoassumeamoreplanarconformation,shiftingthepositionofHisF8andFhelix.HbundergoesastructuralchangeonbindingO2

（2）liguofuAllostericproteinisoneinwhichthebindingofaligandtoonesiteaffectsthebindingpropertiesofanothersiteonthesameprotein.Modulatorisa