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Article
Analyzing the Binding of Co(II)-specific Inhibitors to the Methionyl Aminopeptidases from Escherichia coli and Pyrococcus furiosus
Journal of Biological Inorganic Chemistry
  • Sanghamitra Mitra, Loyola University Chicago
  • George Sheppard, Abbott Laboratories
  • Jieyi Wang, Abbott Laboratories
  • Brian Bennett, Marquette University
  • Richard C. Holz, Marquette University
Document Type
Article
Language
eng
Format of Original
13 p.
Publication Date
5-1-2009
Publisher
Springer
Original Item ID
doi: 10.1007/s00775-009-0471-2; PubMed Central: PMCID 2678238
Disciplines
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

Accepted version. Journal of Biological Inorganic Chemistry, Vol.14, No. 4 (May 2009): 573-585. DOI. © 2009 Springer. Used with permission.

The final publication is available at Springer via http://dx.doi.org/10.1007/s00775-009-0471-2.

Brian Bennett was affiliated with Medical College of Wisconsin at the time of publication.

Richard Holz was affiliated with Loyola University-Chicago at the time of publication.

Citation Information
Sanghamitra Mitra, George Sheppard, Jieyi Wang, Brian Bennett, et al.. "Analyzing the Binding of Co(II)-specific Inhibitors to the Methionyl Aminopeptidases from Escherichia coli and Pyrococcus furiosus" Journal of Biological Inorganic Chemistry (2009) ISSN: 0949-8257
Available at: http://works.bepress.com/richard_holz/98/