Physical Sciences and Mathematics Commons^™

Analyzing The Binding Of Co(Ii)-Specific Inhibitors To The Methionyl Aminopeptidases From Escherichia Coli And Pyrococcus Furiosus, Sanghamitra Mitra, George Sheppard, Jieyi Wang, Brian Bennett, Richard C. Holz

Chemistry Faculty Research and Publications

Methionine aminopeptidases (MetAPs) represent a unique class of protease that is capable of the hydrolytic removal of an N-terminal methionine residue from nascent polypeptide chains. MetAPs are physiologically important enzymes; hence, there is considerable interest in developing inhibitors that can be used as antiangiogenic and antimicrobial agents. A detailed kinetic and spectroscopic study has been performed to probe the binding of a triazole-based inhibitor and a bestatin-based inhibitor to both Mn(II)- and Co(II)-loaded type-I (Escherichia coli) and type-II (Pyrococcus furiosus) MetAPs. Both inhibitors were found to be moderate competitive inhibitors. The triazole-type inhibitor was found to …