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Publication-Lamango



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PRINCIPAL INVESTIGATOR Nazarius Lamango Ph D College of Pharmacy and Pharmaceutical Sciences 1515 South Martin Luther King Jr Blvd Frederick S Humphries Science Research Center Suite 209 G Florida A M University Tallahassee FL 32307 Telephone 850 412 7377 E mail nazarius lamango famu edu Research Significance of Esterases in Prenylation Biochemistry Regular Score Project Prenylation and subsequent S adenosyl L methionine SAM dependent methylation are essential secondary modifications for the biological activity of a significant proportion of eucaryotic proteins Proteins such as the G protein subunits of G protein coupled receptors nuclear lamins some receptors and enzymes and monomeric guanine nucleotide binding proteins such as the Ras and Rab related proteins are prenylated and undergo SAM dependent methylation by prenylated protein methyl transferase PPMTase Prenylated methylated protein methyl esterase PMPMEase readily hydrolyses the methyl esters forming the unmethylated proteins and methanol The importance of the prenylation on protein protein interactions has been demonstrated by the presence of an isoprenyl binding pocket on Rho dissociation inhihibitor Also knockout mice lacking PPMTase activity did not survive through mid gestation The implications of aberrant prenylated protein metabolism on health are therefore enormous The significance of PMPMEase in the pathway remains to be determined We have synthesized a specific UV detectable high affinity small molecule substrate Benzoyl GlycylFarnesyICysteine Methyl ester BzGFCM for the assay of PMPMEase PMPMEase hydrolyses BzGFCM in a time and concentration dependent manner PMPMEase is inhibited by submicromolar concentrations of organophosphorus pesticides OPs and phenylmethylsulfonylfluoride PMSF which are mechanism based inactivators of various serine hydrolases PMPMEase has neither been properly characterized nor purified thus making its physiological and possible clinical relevance even less understood The



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