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.
Available at: http://works.bepress.com/richard_holz/9/
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.
Shareable Link. Provided by the Springer Nature SharedIt content-sharing initiative.