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1、AdvancesinEnzymologyandRelatedAreasofMolecularBiology,Volume62EditedbyAltonMeisterCopyright?1989byJohnWiley&Sons,Inc.REGULATIONOFESCHERICHIACOLIGLUTAMINESYNTHETASEBySUEGOORHEE,P.BOONCHOCK,andEARLR.STADTMAN,LaboratoryofBiochemistry,NationalHeart,Lung,andBloodInst
2、itute,NationalInstitutesofHealth,Bethesda,Maryland20892CONTENTSI.Introduction11.MolecularPropertiesofGlutamineSynthetaseA.AminoAcidSequenceandMolecularStructureB.AdenylylatedandDeadenylylatedFormsC.RolesofDivalentMetalIonsD.TopographicalAnalysisE.KineticProperti
3、esandReactionMechanism111.RegulationofEnzymicActivityA.CumulativeFeedbackControlB.BicyclicCascadeControlC.BicyclicPost-translationalModifcationIsLinkedtoTranscriptionalRegulationofGSD.RolesofATaseandUTaseintheBiosynthesisofGSE.AllostericRegulationofGSCascadeF.In
4、tracellularTurnoverofGSAcknowledgmentsReferencesI.IntroductionGlutaminesynthetase(GS)catalyzesthesynthesisofglutaminefromATP,glutamate,andammonia.Sincetheamidenitrogenatomofglutamineisthepreferrednitrogensourceforthebiosynthesisofvirtuallyallaminoacids,purineand
5、pyrimidinenucleotides,glu-cosamine-6-phosphate,andNAD,GSisasingularlyimportanten-zymeinnitrogenmetabolism;thisisparticularlysoinbacteriawhichsynthesizetheirownaminoacidsandwhereammoniaisthemajorsourceofnitrogen(1).GS,therefore,linkstheassimilationofam-3738S.RHEE
6、,P.CHOCKANDE.STADTMANmoniawithdiversebiosyntheticprocesseswhichultimatelyleadtotheformationofproteins,nucleicacids,complexpolysaccharides,anddifferentcoenzymes.Inviewofitsrole,GSisexpectedtoundergorigorouscellularcontrol;forthisreasontheenzymehasbeenthesubjectof
7、numerousstudies(forreviews,seereferences2-7).ExtensiveinvestigationoftheEscherichiucoliGShasrevealedanumberofimportantregulatorymechanisms.Theseincludethecumulativefeedbackcontrol(2),regulationbyacycliccascademechanism(7,8),oxidativeinactivationofenzymeandintrac
8、ellularproteinturnover(9,10),andthecontrolofproteinsynthesis(4).InthischapterwewillreviewbrieflythemolecularpropertiesandtheregulationoftheE.coliGS,withemphasisonrece