研究生导师介绍姓名：丁焕根性别:男院系：检验医学院、生命科学学院行政职务：专业技术职称：教授任职年月：从事专业1：遗传学从事专业2：导师类别：博士生导师(学术型)最后学历：最后学位：博士任硕导年月：2006任博导年月：2006是否院士：否是否国务院学科评议组成员：否毕业院校：美国宾夕法尼亚大学毕业专业：071010生物化学与分子生物学毕业时间：办公电话：E-mail：hding@lsu.edu在职信息：在岗◇本人从事的主要研究方向的特点、意义及其水平:ResearchProjectsBiogenesisofIron-SulfurProteinsIron-sulfurclustersareubiquitousinbiology.Throughoutevolution,iron-sulfurclustershavebecomeintegralpartsofdiversephysiologicalfunctionsincludingenergyconversion,nitrogenfixation,photosynthesis,intracellularironhomeostasis,heme,biotinandlipoicacidbiosynthesis,RNAmodificationandproteintranslation,DNAreplicationandrepair,andgeneexpressionregulation.Deficiencyoftheiron-sulfurclusterassemblyhasbeenattributedtoanumberofhumandiseases.InEscherichiacoli,atleastsixproteinsencodedbythegeneclusteriscSUA-hscBA-fdxhavebeenidentifiedasessentialforthegeneralbiogenesisofiron-sulfurclusters.IscSisacysteinedesulfurasethatcatalyzesdesulfurizationofL-cysteineandtransferssulfidefortheiron-sulfurclusterassembly.IscUisascaffoldproteinthatassemblesatransientiron-sulfurclusterandtransferstheassembledclusterstotargetproteins.IscAwascharacterizedasanalternativescaffold/carrierproteinfortheiron-sulfurclusterassembly.However,unlikeIscU,IscAhasauniqueironbindingactivitythatcanprovidetheironfortheiron-sulfurclusterassemblyinIscU.HscBandHscAaretwoheatshockcognateproteinsthathavespecificinteractionswiththescaffoldproteinIscUtopromotetheiron-sulfurclustertransferfromIscUtotargetproteins.Ferredoxinislikelyinvolvedintheelectrontransferforthereductiveformationofa[4Fe-4S]clusterinIscU.Inaddition,E.colihasanothergeneclustersufABCDSEfortheiron-sulfurclusterassemblyunderoxidativestressorironstarvationconditions.AmongtheproteinsencodedbythegeneclustersufABCDSE,SufAisahomologofIscAwithsimilarstructureandfunction.WhiledeletionofIscAorSufAhasonlyamildeffectontheiron-sulfurclusterassemblyandcellgrowth,deletionofbothIscAandSufAresultsinanull-growthphenotypeofE.coliinM9minimalmediumunderaerobicgrowthconditions.SufBCDformaproteincomplexthatmayactasascaffoldfortheiron-sulfurclusterassembly.SufSisahomologofIscS.AlthoughSufShasarelativelylowcysteinedesulfuraseactivity,bindingofSufEandSufBCDcomplextoSufScandramaticallystimulatethecysteinedesulfuraseactivityinvitro.WhiletheproteinsencodedbythegeneclusteriscSUA-hscBA-fdxarehighlyconservedfrombacteriatoeukaryoticorganismsincludinghumans,theproteinsencodedbythegeneclustersufABCDSEareonlyfoundinchloroplastsinplantsandinseveralbacteria.Ourresearchhasbeenfocusingonthemolecularmechanismonhowtheintracellularironmayberecruitedandtransferredfortheiron-sulfurclusterassemblyinproteins.WeproposetotestahypothesisthattheprimaryfunctionofIscAistorecruitintracellularironanddelivertheironforthebiogenesisofiron-sulfurclusters.WearealsointerestedintheeffectofothermetalsontheironbindinginIscAandonthebiogenesisofiron-sulfurclustersingeneral.NitricOxideCytotoxicityandIron-SulfurProteinsWhileiron-sulfurclustersareubiquitous,theyarealsohighlysensitivetoreactiveoxygenspeciesandnitrogenspecies.Thesecondprojectinthislaboratoryistounderstandtheredoxreactionunderlyingthemodificationofiron-sulfurclustersinproteinsbynitricoxide(NO)andhowtheNO-modifiediron-sulfurproteinsarerepairedincells.NOisproducedinactivatedmacrophagesandneutrophilsandactsasapowerfulweaponforkillingpathogenicbacteriaandtumorcells.AnexcessiveproductionofNOhasalsobeenimplicatedincausingneurodegenerativedisorders,cardiovasculardiseases,andcancers.However,specificcellulartargetsofNOhavenotbeenfullyunderstood.Recentstudiesfromthislaboratoryandfromresearchothergroupshavedemonstratedthatiron-sulfurclustersaretheprimarytargetofNOincells.UponexposuretoNOatconcentrationsthatemulatethepathophysiologicalproductionsinactivatedmacrophages,alargenumberofiron-sulfurproteinsincellsaremodifiedformingtheprotein-bounddinitrosylironcomplexeswithconcomitantinactivationoftheproteins.Modificationofiron-sulfurproteinsinE.colicellsbyNOresultsinashortdelayofcellgrowthunderaerobicgrowthconditionsandaprolongedbacteriostasisunderanaerobicgrowthconditions.Interestingly,whiletheNO-modifiedprotein-bounddinitrosylironcomplexesarestableinvitro,theyareefficientlyrepairedinE.colicellsunderaerobicconditions.RecentstudiesfromthislaboratoryhaverevealedthatL-cysteine,butnotglutathioneorN-acetyl-L-cysteine,isamajorcellularfactorthatcandecomposetheprotein-bounddinitrosylironcomplex.Inaddition,oxygenappearstobeessentialfortheL-cysteine-mediateddecompositionoftheprotein-bounddinitrosylironcomplexes.Furthermore,theiron-sulfurclusterassemblymachineryisrequiredforacompletere-activationoftheNO-modifiediron-sulfurproteinsinE.colicells.Ourcurrentresearchhasbeenfocusedontheredoxreactionsunderlyingthedecompositionoftheprotein-bounddinitrosylironcomplexes,andonthephysiologicalrolesofL-cysteineandoxygenincellulardefenseagainstnitricoxidecytotoxicity.◇学术团体任职情况:◇近五年在国内外核心期刊上发表学术论文情况:论文题目刊物名称刊物国家收录情况卷期排名Iron-bindingactivityofhumaniron-sulfurclusterassemblyproteinhIscA1BiochemJ国外SCI2010,428(1)CorrespondingauthorIscA/SufAparaloguesarerequiredforthe[4Fe-4S]clusterassemblyinenzymesofmultiplephysiologicalpathwaysinEscherichiacoliunderaerobicgrowthconditionsBiochemJ国外SCI2009,420(3)CorrespondingauthorRedoxcontroloftheDNAdamage-inducibleproteinDinGhelicaseactivityviaitsiron-sulfurclusterJBioChem国外SCI2009,284(8)CorrespondingauthorReactivityofnitricoxidewiththe[4Fe-4S]clusterofdihydroxyaciddehydratasefromEscherichiacoli.BiochemJ国外SCI2009,417(3)CorrespondingauthorNitricoxide-inducedbacteriostasisandmodificationofiron-sulphurproteinsinEscherichiacoliMolMicrobiol国外SCI2008,70(4)CorrespondingauthorEscherichiacoliFtnAactsasanironbufferforre-assemblyofiron-sulfurclustersinresponsetohydrogenperoxidestressBiometals国外SCI2008,21(6)CorrespondingauthorComplementaryrolesofSufAandIscAinthebiogenesisofiron-sulfurclustersinEscherichiacoliBiochemJ国外SCI2008,409(2)CorrespondingauthorEscherichiacolitopoisomeraseIisanironandzincbindingproteinBiometals国内SCI2011,24(4)CorrespondingauthorIron-sulfurproteinsarethemajorsourceofprotein-bounddinitrosylironcomplexesformedinEscherichiacolicellsundernitricoxidestress.FreeRadicBiolMed国内SCI2011,50(11)CorrespondingauthorInvivoevidencefortheiron-bindingactivityofaniron-sulfurclusterassemblyproteinIscAinEscherichiacoliBiochemJ国外SCI2010,432(3)CorrespondingauthorOxygenisrequiredfortheL-cysteine-mediateddecompositionofprotein-bounddinitrosyl-ironcomplexesFreeRadicBiolMed国外SCI2010,49(2)Correspondingauthor◇出版专著教材情况(注：在书名后注明教材或专著):名称类别出版单位日期排名◇成果获奖情况:成果名称颁奖部门等级完成日期证书号排名铁硫簇合成机制与铁硫蛋白功能及应用研究省部一等奖1101011-1第二

◇近五完成的科研项目:项目名称任务来源完成形式完成日期鉴定验收单位主要结论排名
◇目前承担的主要项目:项目名称及下达编号项目类别项目来源起讫时间科研经费(万元)本人承担任务线粒体蛋白mitoNEET对锌与铁硫簇结合功能研究2012-01至2014-1210项目指导锌和铁对大肠杆菌TopA和人类Top3A拓扑异构酶活性的调节机制研究(31100576)2012-01至2014-1220项目指导