Proteins with Complex Architecture as Potential Targets for Drug Design A Case Study of Mycobacterium tuberculosis 英文参考文献.docVIP

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Proteins with Complex Architecture as Potential Targets for Drug Design A Case Study of Mycobacterium tuberculosis 英文参考文献.doc

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Proteins with Complex Architecture as Potential Targets for Drug Design A Case Study of Mycobacterium tuberculosis 英文参考文献

ProteinswithComplexArchitectureasPotentialTargets forDrugDesign:ACaseStudyofMycobacterium tuberculosis Ba′lintMe′sza′ros1,JuditTo′th1,Bea′taG.Ve′rtessy1,2,ZsuzsannaDoszta′nyi1*,Istva′nSimon1* 1Institute of Enzymology, Hungarian Academy of Sciences, Budapest, Hungary, 2Department of Applied Biotechnology, Budapest University of Technology and Economics,Budapest,Hungary Abstract Lengthyco-evolutionofHomosapiensandMycobacteriumtuberculosis,themaincausativeagentoftuberculosis,resultedin adramaticallysuccessfulpathogenspeciesthatpresentsconsiderablechallengeformodernmedicine.Thecontinuousand everincreasingappearanceofmulti-drugresistantmycobacterianecessitatestheidentificationofnoveldrugtargetsand drugswithnewmechanismsofaction.However,furtherinsightsareneededtoestablishautomatedprotocolsfortarget selectionbasedontheavailablecompletegenomesequences.Inthepresentstudy,weperformcompleteproteomelevel comparisonsbetweenM.tuberculosis,mycobacteria,otherprokaryotesandavailableeukaryotesbasedonproteindomains, local sequence similarities and protein disorder. We show that the enrichment of certain domains in the genome can indicateanimportantfunctionspecifictoM.tuberculosis.Weidentifiedtwofamilies,termedpknandPE/PPEthatstandout in this respect. The common property of these two protein families is a complex domain organization that combines species-specific regions, commonly occurring domains and disordered segments. Besides highlighting promising novel drug target candidates in M. tuberculosis, the presented analysis can also be viewed as a general protocol to identify proteinsinvolvedinspecies-specificfunctionsinagivenorganism.Weconcludethattargetselectionprotocolsshouldbe extendedtoincludeproteinswithcomplexdomainarchitecturesinsteadoffocusingonsequentiallyuniqueandessential proteinsonly. Citation:Me′sza′rosB,To′thJ,Ve′rtessy BG,Doszta′nyiZ,SimonI(2011)ProteinswithComplexArchitectureasPotentialTargetsforDrugDesign:ACaseStudyof Mycobacteriumtuberculosis.PLoSComputBiol7(7):e1