Hydroxamate Inhibitor Profiling of Both Zn2+- and Ni2+-Activated Glyoxalase I Metalloenzymes Having Diverse Quaternary Structures

Title:Hydroxamate Inhibitor Profiling of Both Zn2+- and Ni2+-Activated Glyoxalase I Metalloenzymes Having Diverse Quaternary Structures

Volume: 14 Issue: 7

Author(s): Uthaiwan Suttisansanee and John F. Honek*

Affiliation:

• Department of Chemistry, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada N2L 3G1,Canada

Keywords: Glyoxalase, nickel, zinc, inhibitor, hydroxamate, metalloenzyme, Clostridium, Pseudomonas, Saccharomyces.

Abstract: Background: The glyoxalase enzyme system is a critical component in the detoxification of cellular metabolically generated alpha-ketoaldehydes, such as methylglyoxal. Inhibitors of these enzymes have been shown to have potential in the development of antimicrobial and antitumor agents. A number of glyoxalase I (Glo1) metalloenzymes have been identified and have been categorized as either Zn2+-activated or Ni2+-activated metalloenzymes.

Method: In the current work, four Glo1 from both metal activation classes and also having different quaternary structures were screened against two prototypic hydroxamate-containing peptide inhibitors in order to provide preliminary information on inhibition characteristics for these diverse metalloenzymes.

Conclusion: This information should prove useful in future inhibitor design initiatives to develop more potent and organism selective Glo1 inhibitors.

Cite this article as:

Suttisansanee Uthaiwan and Honek F. John*, Hydroxamate Inhibitor Profiling of Both Zn2+- and Ni2+-Activated Glyoxalase I Metalloenzymes Having Diverse Quaternary Structures, Letters in Drug Design & Discovery 2017; 14 (7) . https://dx.doi.org/10.2174/1570180814666161128115808

DOI https://dx.doi.org/10.2174/1570180814666161128115808	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X