Sequence Alignment Reveals Possible MAPK Docking Motifs on HIV Proteins 英文参考文献.docVIP

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Sequence Alignment Reveals Possible MAPK Docking Motifs on HIV Proteins 英文参考文献.doc

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Sequence Alignment Reveals Possible MAPK Docking Motifs on HIV Proteins 英文参考文献

SequenceAlignmentRevealsPossibleMAPKDocking MotifsonHIVProteins PerryEvans1,AhmetSacan2,LyleUngar1,AydinTozeren2* 1GenomicsandComputationalBiologyandDepartmentofComputerandInformationScience,UniversityofPennsylvania,Philadelphia,Pennsylvania,UnitedStatesof America, 2Center for Integrated Bioinformatics, School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, United StatesofAmerica Abstract OverthecourseofHIVinfection,virusreplicationisfacilitatedbythephosphorylationofHIVproteinsbyhumanERK1and ERK2mitogen-activatedproteinkinases(MAPKs).MAPKsareknowntophosphorylatetheirsubstratesbyfirstbindingwith them at adocking site. Docking site interactions could be viable drug targets because thesequences guiding them are morespecificthanphosphorylationconsensussites.Inthisstudyweusemultiplebioinformaticstoolstodiscovercandidate MAPK docking site motifs on HIV proteins known to be phosphorylated by MAPKs, and we discuss the possibility of targetingdockingsiteswithdrugs.UsingsequencealignmentsofHIVproteinsofdifferentsubtypes,weshowthatMAPK docking patterns previously described for human proteins appear on the HIV matrix, Tat, and Vif proteins in a strain dependentmanner,butareabsentfromHIVRevandappearonallHIVNefstrains.Werevisetheregularexpressionsof previously annotated MAPK docking patterns in order to provide a subtype independent motif that annotates all HIV proteins. One revision is based on a documented human variant of one of the substrate docking motifs, and the other reducesthenumberofrequiredbasicaminoacidsinthestandarddockingmotifsfromtwotoone.Theproposedpatterns areshowntobeconsistentwithinsilicodockingbetweenERK1andtheHIVmatrixprotein.ThemotifusageonHIVproteins issufficientlydifferentfromhumanproteinsinaminoacidsequencesimilaritytoallowforHIVspecifictargetingusingsmall- moleculedrugs. Citation: Evans P, Sacan A, Ungar L, Tozeren A (2010) Sequence Alignment Reveals Possible MAPK Docking Motifs on HIV Proteins. PLo