A Computational Study of a Recreated G Protein-GEF Reaction Intermediate Competent for Nucleotide Exchange Fate of the Mg Ion 英文参考文献.docVIP

下载本文档

3
0
约5.04万字
约 10页
2017-05-11 发布于上海
举报
版权申诉

A Computational Study of a Recreated G Protein-GEF Reaction Intermediate Competent for Nucleotide Exchange Fate of the Mg Ion 英文参考文献.doc

1、本文档共10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

A Computational Study of a Recreated G Protein-GEF Reaction Intermediate Competent for Nucleotide Exchange Fate of the Mg Ion 英文参考文献

AComputationalStudyofaRecreatedGProtein-GEF ReactionIntermediateCompetentforNucleotide Exchange:FateoftheMgIon Me′riamBenHamida-Reba?¨,CharlesH.Robert*¤ CNRSInstituteofBiochemistryandMolecularandCellularBiology(IBBMC),Universite′ Paris-Sud11,Orsay,France Abstract SmallG-proteinsofthesuperfamilyRasfunctionasmolecularswitches,interactingwithdifferentcellularpartnersaccording to their activation state. G-protein activation involves the dissociation of bound GDP and its replacement by GTP, in an exchange reaction that is accelerated and regulated in the cell by guanine-nucleotide exchange factors (GEFs). Large conformationalchangesaccompanytheexchangereaction,andourunderstandingofthemechanismiscorrespondingly incomplete.However,muchknowledgehasbeenderivedfromstructuralstudiesofblockedorinactivemutantGEFs,which presumablycloselyrepresentintermediatesintheexchangereactionandyetwhicharebydesignincompetentforcarrying out the nucleotide exchange reaction. In this study we have used comparative modelling to recreate an exchange- competent form of a late, pre-GDP-ejection intermediate species in Arf1, a well-characterized small G-protein. We extensivelycharacterizedthreedistinctmodelsofthisintermediateusingmoleculardynamicssimulations,allowingusto address ambiguities related to the mutant structural studies. We observed in particular the unfavorable nature of Mg2z associatedformsofthecomplexandtheestablishmentofcloserArf1-GEFcontactsinitsabsence.Theresultsofthisstudy shedlightonGEF-mediatedactivationofthissmallGproteinandonpredictingthefateoftheMgionatacriticalpointin the exchange reaction. The structural models themselves furnish additional targets for interfacial inhibitor design, a promisingdirectionforexploringpotentiallydruggabletargetswithhighbiologicalspecificity. Citation: Ben Hamida-Reba?¨ M, Robert CH (2010) A Computational Study of a Recreated G Protein-GEF Reaction Intermediate Competent for Nucleotide Exchange:FateoftheMgIon.PLoSONE5(2):e9142.doi:10.1371/jo