zhang j liu hc zhu kk gong药化生药学谢.pdfVIP

Antiinfectivetherapywithasmall

moleculeinhibitorof

Staphylococcusaureussortase

作者：Zhang,J(Zhang,Jie);Liu,HC(Liu,

Hongchuan);Zhu,KK(Zhu,Kongkai);Gong,SZ(Gong,

Shouzhe);Dramsi,S(Dramsi,Shaynoor);Wang,

YT(Wang,Ya-Ting);Li,JF(Li,Jiafei);Chen,FF(Chen,

Feifei);Zhang,RH(Zhang,Ruihan);Zhou,L(Zhou,Lu)

•：PROCEEDINGSOFTHENATIONAL

ACADEMYOFSCIENCESOFTHEUNITED

STATESOFAMERICA（院刊）

•时间:2014/09/16

•SCI分区：2

•影响因子：9.809

•Methicillin-resistantStaphylococcus

aureus耐甲氧西林金葡萄球菌

•virtualscreening虚拟筛选

•optimizationofinhibitorstructure抑制剂结

构优化

•SurfaceproteinsofS.aureusaresecretedasprecursors

withC-terminalsortingsignalsthatarecleavedbysortase

Abetweenthethreonine(T)andtheglycine(G)residuesof

theirLPXTGmotif.Theactivesitecysteineresidueof

sortaseformsanacylenzymeintermediatethatisrelieved

bythenucleophilicattackoftheaminogroupin

peptidoglycansynthesisprecursors.Surfaceproteins

attachedtopeptidoglycanprecursorsaresubsequently

incorporatedintothecellwallenvelopeanddisplayedon

thestaphylococcalsurface(9).Genomesequencing

revealedthatallS.aureusisolatesencode17–21surface

proteinswithLPXTGsortingsignals,whichfulfilldiverse

functionsduringtheinfectiousprocess.SrtAmutants

cannotassemblesurfaceproteinsintotheirenvelopeand

areunabletoformabscesslesionsinorgantissuesor

causelethalbacteremiawheninoculatedintothe

bloodstreamofmice.Incontrast,mutationsthatabrogate

theexpressionofsecretedvirulencefactorsmaycause

attenuationbutdonotabrogatetheabilityofS.aureusto

causeinfectiousdiseases.

•IdentifyingSortaseInhibitors.We