细菌多药外排系统及其研究方法的进展

《细菌多药外排系统及其研究方法的进展》由会员上传分享，免费在线阅读，更多相关内容在应用文档-天天文库。

1、细菌多药外排系统及其研究方法的进展【摘要】位于细菌细胞膜上的多药外排泵可将多种结构无关药物排出，本文综述了细菌主要外排泵包括初级和次级转运系统的分子生物学特征及外排蛋白结构与药物识别和转运上的关系；同时总结了对外排蛋白进行结构与功能关系研究的主要的方法，包括定点诱变、螺旋空间排列和结晶等。【关键词】细菌外排泵多药耐药IntroductionTheproblemofdrugresistanceisamainobstacleinthestrugglebetanbEingandinfectiousdiseases.Oneofthemostimportantbacterialresist

2、antmechanismsisthemultidrugeffluxpumpssituatedonthemembranes,ajortypesbasedontheenergysource:primarytransportsystem,suchasATPbindingcassette(ABC)transportersuperfamilyutilizestheenergyproducedbyATPhydrolysistoeffluxdiversepounds;pumpsdifferentsubstratesviatheprotonmotiveforce(PMF)providingby

3、transmembraneelectrochemicalprotongradient(ΔμH+)orthesodiummotiveforcesupplyingbyiongradients(ΔμNa+).Despitethetotallydifferentevolutionarytraitandenergysources,bothcantransportabroadspectrumofstructurallyunrelatedsubstrates.Todate,duetothehighlyhydrophobicnature,thecrystallizationofthestruct

4、ureonmostofthemembranetransportersisyettobecrackeddoostimportantanalysisapproachisstillproteinengineeringmethodsinvolvingsitedirectedmutagenesisandchemicalmodification.Andcurrentlytherehavedevelopedsomeimprovementsonthesemethods.BacterialmultidrugeffluxpumpsystemsATPbindingcassette(ABC)tran

5、sporterTodate,LmrAistheonlyosomallylocatedlmrAgeneinLactococcuslactis.Ingeneral,activeABCproteinsdemandminimaltembranedomains(TMDs)andtain,NBD).Theformerusuallyconsistsofsixtransmembranesegments(αhelices);thelatter,a200～250aminoacids,containsthreeconservedmotifsDNBD)2.paringanmultidrugresis

6、tancePglycoprotein(Pgp),LmrAhasonlytains,buthomologoustoeachofthetodimer,echanismofLmrAstillremainsunclear,tcleanermodelshotheinnerleafletofthemembraneintotheexternalodelsuggeststhatLmrAfirstrecognizessubstratesintheinnerleafletofthemembranethenflipthemtotheouterleafletfromationalchanges,od

7、ulatetheinteractionbetovementofdrugbindingsitefrominnermembranetotheoutsideduetothepreventionofATPhydrolysisattheothersite,sothedrugscanbetranslocatedbetsatransportcycle［5］.Sofar,theconfirmedsubstratesofLmrAincludeanticancerdrugs(vincaalkalo