Analyzing the Binding of Co(II)-specific Inhibitors to the Methionyl Aminopeptidases from Escherichia coli and Pyrococcus furiosus
Journal of Biological Inorganic Chemistry
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 interact with both active-site metal ions, while the bestatin-type inhibitor was capable of switching its mode of binding depending on the metal in the active site and the type of MetAP enzyme.
Mitra, Sanghamitra; Sheppard, George; Wang, Jieyi; Bennett, Brian; and Holz, Richard C., "Analyzing the Binding of Co(II)-specific Inhibitors to the Methionyl Aminopeptidases from Escherichia coli and Pyrococcus furiosus" (2009). Chemistry Faculty Research and Publications. 280.
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Accepted version. Journal of Biological Inorganic Chemistry, Vol. 14, No. 4 (May 2009): 573-585. DOI. © 2009 Springer Nature Switzerland AG. Part of Springer Nature. Used with permission.
Richard C. Holz was affiliated with Loyola University-Chicago at the time of publication.
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