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Molecular Discrimination Of Type-I Over Type-Ii Methionyl Aminopeptidases, Krzysztof Swierczek, Alicja J. Copik, Sabina I. Swierczek, Richard C. Holz
Molecular Discrimination Of Type-I Over Type-Ii Methionyl Aminopeptidases, Krzysztof Swierczek, Alicja J. Copik, Sabina I. Swierczek, Richard C. Holz
Chemistry Faculty Research and Publications
Two residues that are conserved in type-I methionyl aminopeptidases (MetAPs) but are absent in all type-II MetAPs are the cysteine residues (Escherichia coli MetAP-I: C59 and C70) that reside at the back of the substrate recognition pocket. These Cys residues are 4.4 Å apart and do not form a disulfide bond. Since bacteria and fungi contain only type-I MetAPs while all human cells contain both type-I and type-II MetAPs, type-I MetAPs represent a novel antibiotic/antifungal target if type-I MetAPs can be specifically targeted over type-II. Based on reaction of the thiol-specific binding reagent 5,5‘-dithio-bis(2-nitrobenzoic acid) (DTNB) with the type-I …