Title
Analyzing the Binding of Co(II)-specific Inhibitors to the Methionyl Aminopeptidases from Escherichia coli and Pyrococcus furiosus
Document Type
Article
Publication Date
5-2009
Source Publication
Journal of Biological Inorganic Chemistry
Source ISSN
0949-8257
Abstract
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.
Comments
Journal of Biological Inorganic Chemistry, Vol. 14, No. 4 (May 2009): 573-585. DOI.
Richard C. Holz was affiliated with Loyola University-Chicago at the time of publication.