Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum 英文参考文献.docVIP

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Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum 英文参考文献.doc

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Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum 英文参考文献

FingerprintingtheSubstrateSpecificityofM1andM17 AminopeptidasesofHumanMalaria,Plasmodium falciparum MarcinPoreba1,SheenaMcGowan2,3,TinaS.Skinner-Adams4,5,6,KatharineR.Trenholme4,5,6 DonaldL.Gardiner4,5,6,JamesC.Whisstock2,3,JoyceTo7,GuyS.Salvesen8,JohnP.Dalton7*, MarcinDrag1,8 , * 1Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wroclaw University of Technology, Wroclaw, Poland, 2Department of Biochemistry and MolecularBiologyandAustralianResearchCouncilCentreofExcellenceinStructuralandFunctionalMicrobialGenomics,MonashUniversity,Clayton,Victoria,Australia, 3Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia, 4Malaria Biology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia, 5Griffith Medical Research College, Joint Program of Griffith University and the Queensland Institute of Medical Research, Brisbane,Queensland,Australia,6SchoolofMedicine,TheUniversityofQueensland,RoyalBrisbaneHospital,Brisbane,Queensland,Australia,7InstituteofParasitology, McGill University, Sainte Anne de Bellevue, Quebec, Canada, 8Program in Apoptosis and Cell Death Research, Sanford Burnham Medical Research Institute, La Jolla, California,UnitedStatesofAmerica Abstract Background:Plasmodiumfalciparum,thecausativeagentofhumanmalaria,expressestwoaminopeptidases,PfM1AAPand PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis,growthanddevelopment.Theseexopeptidasesarepotentialtargetsforthedevelopmentofanewclassofanti- malariadrugs. Methodology/Principal Findings: To define the substrate specificity of recombinant forms of these two malaria aminopeptidasesweusedanewlibraryconsistingof61fluorogenicsubstratesderivedbothfromnaturalandunnatural aminoacids.WeobtainedadetailedsubstratefingerprintforrecombinantformsoftheenzymesrevealingthatPfM1AAP exhibitsaverybroadsubstratetolerance,capableofefficientlyhydrolyzingneu