Dissecting the Role of Critical Residues and Substrate Preference of a Fatty Acyl-CoA Synthetase (FadD13) of Mycobacterium tuberculosis 英文参考文献.docVIP

下载本文档

5
0
约7.21万字
约 15页
2017-05-11 发布于上海
举报
版权申诉

Dissecting the Role of Critical Residues and Substrate Preference of a Fatty Acyl-CoA Synthetase (FadD13) of Mycobacterium tuberculosis 英文参考文献.doc

1、本文档共15页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

Dissecting the Role of Critical Residues and Substrate Preference of a Fatty Acyl-CoA Synthetase (FadD13) of Mycobacterium tuberculosis 英文参考文献

DissectingtheRoleofCriticalResiduesandSubstrate PreferenceofaFattyAcyl-CoASynthetase(FadD13)of Mycobacteriumtuberculosis GarimaKhare1,VibhaGupta1,RakeshK.Gupta1,2,RadhikaGupta1,RajivBhat3,AnilK.Tyagi1* 1Department of Biochemistry, University of Delhi South Campus, New Delhi, India, 2Department of Microbiology, Ram Lal Anand College, University of Delhi South Campus,NewDelhi,India,3SchoolofBiotechnology,JawaharlalNehruUniversity,NewDelhi,India Abstract Newly emerging multi-drug resistant strains of Mycobacterium tuberculosis (M.tb) severely limit the treatment options for tuberculosis(TB);hence,newantituberculardrugsareurgentlyneeded.ThemymAoperonisessentialforthevirulenceand intracellularsurvivalofM.tbandthusrepresentsanattractivetargetforthedevelopmentofnewantituberculardrugs.This studyisfocusedonthestructure-functionrelationshipofFattyAcyl-CoASynthetase(FadD13,Rv3089)belongingtothemymA operon.Eightsite-directedmutantsofFadD13weredesigned,constructedandanalyzedforthestructural-functionalintegrity oftheenzyme.ThestudyrevealedthatmutationofLys487resultedin,95%lossoftheactivitythusdemonstratingitscrucial requirementfortheenzymaticactivity.ComparisonofthekineticparametersshowedtheresiduesLys172andAla302tobe involvedinthebindingofATPandSer404inthebindingofCoenzymeA.TheinfluenceofmutationsoftheresiduesVal209 and Trp377emphasizedtheirimportanceinmaintainingthestructuralintegrityofFadD13.Besides,weshowasynergisticinfluence of fatty acid and ATP binding on the conformation and rigidity of FadD13. FadD13 represents the first Fatty Acyl-CoA Synthetasetodisplaybiphasickineticsforfattyacids.FadD13exhibitsadistinctpreferenceforC26/C24fattyacids,whichinthe lightofearlierreportedobservationsfurthersubstantiatestheroleofthemymAoperoninremodelingthecellenvelopeof intracellularM.tbunderacidicconditions.Athree-dimensionalmodelofFadD13wasgenerated;thedockingofATPtothe active site verified its interaction with Lys172, Ala302 and Lys487 and corresponded well withthe results of the muta