Mycobacterium tuberculosis Rv3802c Encodes a PhospholipaseThioesterase and Is Inhibited by the Antimycobacterial Agent Tetrahydrolipstatin 英文参考文献.docVIP

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Mycobacterium tuberculosis Rv3802c Encodes a PhospholipaseThioesterase and Is Inhibited by the Antimycobacterial Agent Tetrahydrolipstatin 英文参考文献.doc

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Mycobacterium tuberculosis Rv3802c Encodes a PhospholipaseThioesterase and Is Inhibited by the Antimycobacterial Agent Tetrahydrolipstatin 英文参考文献

MycobacteriumtuberculosisRv3802cEncodesa Phospholipase/ThioesteraseandIsInhibitedbythe AntimycobacterialAgentTetrahydrolipstatin SarahK.Parker1*,RobertM.Barkley3,JohnG.Rino1,MichaelL.Vasil2 1DepartmentofPediatrics,UniversityofColoradoDenver,Aurora,Colorado,UnitedStatesofAmerica,2DepartmentofMicrobiology,UniversityofColoradoDenver, Aurora,Colorado,UnitedStatesofAmerica,3DepartmentofPharmacology,UniversityofColoradoDenver,Aurora,Colorado,UnitedStatesofAmerica Abstract ThecellwallofM.tuberculosisiscentraltoitssuccessasapathogen.Mycolicacidsarekeycomponentsofthiscellwall.The genesinvolvedinjoiningtheaandmeromycolatesarelocatedinacluster,beginningwithRv3799candextendingatleast untilRv3804c.Theroleofeachenzymeencodedbythesefivegenesisfairlywellunderstood,exceptforRv3802c.Rv3802is one of seven putative cutinases encodedby thegenome of M. tuberculosis.In phytopathogens, cutinases hydrolyze the waxylayerofplants,cutin.Inastrictlymammalianpathogen,suchasM.tuberculosis,itislikelythattheseproteinsperforma different function. Of the seven, we chose to focus on Rv3802c because of its location in a mycolic acid synthesis gene cluster,itsputativeessentiality,itsubiquitouspresenceinactinomycetes,anditsconservationintheminimalgenomeof Mycobacteriumleprae.WeexpressedRv3802inEscherichiacoliandpurifiedtheenzymaticallyactiveform.Weprobedits activities and inhibitors characterizing those relevant to its possible role in mycolic acid biosynthesis. In addition to its reported phospholipase A activity, Rv3802 has significant thioesterase activity, and it is inhibited by tetrahydrolipstatin (THL). THL is a described anti-tuberculous compound with an unknown mechanism, but it reportedly targets cell wall synthesis.Takentogether,thesedatacircumstantiallysupportaroleforRv3802inmycolicacidsynthesisand,asthecellwall isintegraltoM.tuberculosispathogenesis,identificationofanovelcellwallenzymeanditsinhibitionhastherapeuticand diagnosticimplications. Citation: Parker SK, Barkley RM, Rino JG, Vasil M