细菌多药外排系统及其研究方法的进展论文

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1、细菌多药外排系统及其研究方法的进展论文.freelofdrugresistanceisamainobstacleinthestrugglebetanbeingandinfectiousdiseases.Oneofthemostimportantbacterialresistantmechanismsisthemultidrugeffluxpumpssituatedonthemembranes,ajortypesbasedontheenergysource:primarytransportsystem,suchasATPbindingcassette(ABC)transp

2、ortersuperfamilyutilizestheenergyproducedbyATPhydrolysistoeffluxdiversepounds;pumpsdifferentsubstratesviatheprotonmotiveforce(PMF)providingbytransmembraneelectrochemicalprotongradient(ΔμH+)orthesodiummotiveforcesupplyingbyiongradients(ΔμNa+).Despitethetotallydifferentevolutionarytraitande

3、nergysources,bothcantransportabroadspectrumofstructurallyunrelatedsubstrates.Todate,duetothehighlyhydrophobicnature,thecrystallizationofthestructureonmostofthemembranetransportersisyettobecrackeddoostimportantanalysisapproachisstillproteinengineeringmethodsinvolvingsitedirectedmutagenesi

4、sandchemicalmodification.Andcurrentlytherehavedevelopedsomeimprovementsonthesemethods.BacterialmultidrugeffluxpumpsystemsATPbindingcassette(ABC)transporterTodate,LmrAistheonlyosomallylocatedlmrAgeneinLactococcuslactis.Ingeneral,activeABCproteinsdemandminimaltembranedomains(TMDs)andtain,N

5、BD).Theformerusuallyconsistsofsixtransmembranesegments(αhelices);thelatter,.freelinoacids,containsthreeconservedmotifsDNBD)2.paringanmultidrugresistancePglycoprotein(Pgp),LmrAhasonlytains,buthomologoustoeachofthetodimer,echanismofLmrAstillremainsunclear,tcleanermodelshotheinnerleaflet

6、ofthemembraneintotheexternalodelsuggeststhatLmrAfirstrecognizessubstratesintheinnerleafletofthemembranethenflipthemtotheouterleafletfromationalchanges,odulatetheinteractionbetovementofdrugbindingsitefrominnermembranetotheoutsideduetothepreventionofATPhydrolysisattheothersite,sothedrugsca

7、nbetranslocatedbetsatransportcycle［5］.Sofar,theconfirmedsubstratesofLmrAincludeanticancerdrugs(vincaalkaloidsandanthracyclines),DNAintercalators,toxicpeptides,fluorescentmembraneprobesanddyesasportantantibioticssuchasaminoglycosides,lincosamides,macrolides,quinolone