cytochrome p450 3a4 the impossible protein细胞色素p450 3a4不可能的蛋白

《cytochrome p450 3a4 the impossible protein细胞色素p450 3a4不可能的蛋白》由会员上传分享，免费在线阅读，更多相关内容在教育资源-天天文库。

1、KatrinaBossertJimenezLabCytochromeP4503A4:TheImpossibleProteinIntroductionIthasbeenadifficultexperienceworkingtheliverproteinknownasP4503A4.Thisparticularproteinisfoundinthelivermembranes,andbecauseofitsnaturetoadheretomembranes,theproteinisnotaneasyonetopurify.Whilemostproteinsonlyneeda

2、fewspecificpurificationsteps,IhavehadtheopportunitytoworkwithnearlyeverypurificationtechniquethatIhadlearnedaboutintheBiochemistryclassItookduringmyexperiencewithP450.Ispecificallyremembertheprofessorsayinghedidnotwanttogetintothetopicofmembraneproteinsbecausetheywere“abigmess.”NowIcompl

3、etelyunderstandwhathemeant.ThetechnologyintherealmofopticsandphysicalchemistryhasthepotentialtounlockimportantscientificfactsaboutproteinssuchasP450s.Adrugthatgoesintothebodyisnotalwaysthesameonethatcausestheuseful(orharmful)effects.Forinstance,codeineisturnedintomorphineandbenzeneitself

4、isnotacarcinogenbutintheoxidizedformcreatedbytheP450enzymeitisharmfultohumanDNA.DoctorsandpharmacistsarestillunabletopredicthowcertaindrugswillreactwhenadministeredtogetherbecauseoftheuncertaintyinthewayP450mightreactwithbothofthesedrugsatonce.ItisspeculatedthatthespecificP450,3A4,canbin

5、dtwodrugsatthesametime,andinthissituationthedrugswillnotbeoxidizedinthesamewaythattheywouldbeiftherewereonlyoneboundtotheprotein.Thismakesitdifficulttoadministermorethanonedrugatoncebecauseofthepossibleeffectsthatoccurdueto3A4.Inadditiontohavingthisbindingproperty,3A4isthemostabundantcyt

6、ochromeP450intheliver.Itisveryimportanttodrugmetabolisminhumans,thusmakingitanimportantproteintodoresearchon.II.TheProteinTheproteinP4503A4isoneofthemostabundantP450sintheliver.Itisuniqueinthatithasaparticularlylargebindingcavitywhichcouldpossibleholdmorethanonedrugatonce.Althoughthishas

7、neverbeenproven,thecloselyrelatedbacterialP450eryFhasbeenshownboundtotwoligandsatonce.Itiswhatlieswithinthebindingcavitythatallowstheproteinsbindinghabitstobestudiedmoreindepth.Thefirstkeyfactorinbeingabletodeterminethebindingoftheproteinisthatitcontainsahemegroupinthebin