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

[ Vol. 14 , Issue. 7 ]

Author(s):

Uthaiwan Suttisansanee and John F. Honek*   Pages 843 - 852 ( 10 )

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.

Keywords:

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

Affiliation:

Institute of Nutrition, Mahidol University, 25/25 Phutthamonthon 4 Rd., Salaya, Phutthamonthon, Nakhon Pathom 73170, Department of Chemistry, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada N2L 3G1

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