A Conformational Switch in the Active Site of BT_2972, a Methyltransferase from an Antibiotic Resistant Pathogen B. thetaiotaomicron 英文参考文献.docVIP

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A Conformational Switch in the Active Site of BT_2972, a Methyltransferase from an Antibiotic Resistant Pathogen B. thetaiotaomicron 英文参考文献.doc

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A Conformational Switch in the Active Site of BT_2972, a Methyltransferase from an Antibiotic Resistant Pathogen B. thetaiotaomicron 英文参考文献

AConformationalSwitchintheActiveSiteofBT_2972,a MethyltransferasefromanAntibioticResistantPathogen B.thetaiotaomicron VeerendraKumar,J.Sivaraman* DepartmentofBiologicalSciences,NationalUniversityofSingapore,Singapore,Singapore Abstract Methylationisoneofthemostcommonbiochemicalreactionsinvolvedincellularandmetabolicfunctionsandiscatalysed bytheactionofmethyltransferases.Bacteroidesthetaiotaomicronisanantibiotic-resistantbacteriumthatconfersresistance throughmethylation,andasyet,thereisnoreportonthestructureofmethyltransferasesfromthisbacterium.Here,we reportthecrystalstructureofanAdoMet-dependentmethyltransferase,BT_2972anditscomplexwithAdoMetandAdoHcy for B. thetaiotaomicron VPI-5482 strain along with isothermal titration calorimetric assessment of the binding affinities. ComparisonoftheapoandcomplexedBT_2972structuresrevealsasignificantconformationalchangebetweenopenand closed forms of the active site that presumably regulates the association with cofactors and may aid interaction with substrate.Together,ouranalysissuggeststhatBT_2972isasmallmoleculemethyltransferaseandmightcatalyzetwoO- methylationreactionstepsinvolvedintheubiquinonebiosynthesispathway. Citation: Kumar V, Sivaraman J (2011) A Conformational Switch in the Active Site of BT_2972, a Methyltransferase from an Antibiotic Resistant Pathogen B. thetaiotaomicron.PLoSONE6(11):e27543.doi:10.1371/journal.pone.0027543 Editor:PaulC.Driscoll,MRCNationalInstituteforMedicalResearch,UnitedKingdom ReceivedJuly22,2011;AcceptedOctober19,2011;PublishedNovember28,2011 Copyright:?2011Kumar,Sivaraman.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:TheauthorsaregratefultotheBiomedicalResearchCouncilofSingapore(BMRC),A*STARforprovidingaresearchgrant(R154000362305)tosupport thisstudy.X-raydiffractiondataweremeasuredatbeamlineX-12B1ofNationalSynchrotronRadiat