Repositioning Antimicrobial Agent Pentamidine as a Disruptor of the Lateral Interactions of Transmembrane Domain 5 of EBV Latent Membrane Protein 1 英文参考文献.docVIP

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Repositioning Antimicrobial Agent Pentamidine as a Disruptor of the Lateral Interactions of Transmembrane Domain 5 of EBV Latent Membrane Protein 1 英文参考文献.doc

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Repositioning Antimicrobial Agent Pentamidine as a Disruptor of the Lateral Interactions of Transmembrane Domain 5 of EBV Latent Membrane Protein 1 英文参考文献

RepositioningAntimicrobialAgentPentamidineasa DisruptoroftheLateralInteractionsofTransmembrane Domain5ofEBVLatentMembraneProtein1 XiaohuiWang1,2,ZenoFiorini1,ChristinaSmith1,YingningZhang2,JingLi3*,LindaR.Watkins2, HangYin1* 1DepartmentofChemistryandBiochemistryandBioFrontiersInstitute,UniversityofColoradoatBoulder,Boulder,Colorado,UnitedStatesofAmerica,2Departmentof Psychology and Neuroscience, and the Center for Neuroscience, University of Colorado at Boulder, Boulder, Colorado, United States of America, 3Department of Rheumatology,PekingUnionMedicalCollegeHospital,ChineseAcademyofMedicalSciences,Beijing,People’sRepublicofChina Abstract The lateral transmembrane protein-protein interactions (PPI) have been regarded as ‘‘undruggable’’ despite their importanceinmanyessentialbiologicalprocesses.Thehomo-trimerizationoftransmembranedomain5(TMD-5)oflatent membraneprotein1(LMP-1)iscriticalfortheconstitutiveoncogenicactivationoftheEpstein-Barrvirus(EBV).Hereinwe repurposetheantimicrobialagentpentamidineasaregulatorofLMP-1TMD-5lateralinteractions.TheresultsofToxRassay, tryptophan fluorescence assay, courmarin fluorescence dequenching assay, and Bis-Tris sodium dodecyl sulfate polyacrylamidegelelectrophoresis (SDS)consistentlyshowpentamidinedisrupts LMP-1TMD-5 lateralinteractions. Furthermore,pentamidineinhibitsLMP-1signaling,inducingcellularapoptosisandsuppressingcellproliferationintheEBV infectedBcells.Incontrast,EBVnegativecellsarelesssusceptibletopentamidine.Thisstudyprovidesanovelnon-peptide smallmoleculeagentforregulatingLMP-1TMD-5lateralinteractions. Citation: Wang X, Fiorini Z, Smith C, Zhang Y, Li J, et al. (2012) Repositioning Antimicrobial Agent Pentamidine as a Disruptor of the Lateral Interactions of TransmembraneDomain5ofEBVLatentMembraneProtein1.PLoSONE7(10):e47703.doi:10.1371/journal.pone.0047703 Editor:LuwenZhang,UniversityofNebraska-Lincoln,UnitedStatesofAmerica ReceivedJuly22,2012;AcceptedSeptember14,2012;PublishedOctober19,2012 Copyright: ? 2012 Wa