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

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

Journal Name: Letters in Drug Design & Discovery

Volume 14 , Issue 7 , 2017

Become EABM
Become Reviewer

Graphical Abstract:


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.

Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 14
ISSUE: 7
Year: 2017
Page: [843 - 852]
Pages: 10
DOI: 10.2174/1570180814666161128115808
Price: $58

Article Metrics

PDF: 15
HTML: 2