Kinetic characterization of a slow-binding inhibitor of Bla2: thiomaltol.
Summary of "Kinetic characterization of a slow-binding inhibitor of Bla2: thiomaltol."
The increasing prevalence of drug resistant bacteria is a pandemic problem. Metallo-β-lactamases (MBLs) are one of the main causes of drug resistance due to hydrolysis of β-lactam antibiotics. Thus, the development of effective inhibitors of MBLs remains urgent. The compound thiomaltol was used as a lead compound to investigate its ability to inhibit metallo-β-lactamase from Bacillus anthracis (Bla2), which causes anthrax. Kinetic evaluation with nitrocefin as a substrate indicates that thiomaltol inhibits Bla2 in a time-dependent manner with an IC(50) value of 290 µM after 20 min preincubation. Progress curve analysis and reversibility tests suggest that thiomaltol is a reversible, slow-binding inhibitor with a K(i) of 85 ± 30 µM. Furthermore, studies on the modality of inhibition and in silico analysis indicate thiomaltol to be a competitive inhibitor. The results demonstrate that thiomaltol is a promising lead compound for slow binding inhibitor design of Bla2.
Affiliation
Department of Chemistry and Biochemistry, Baylor University , Waco, TX , USA.
Journal Details
This article was published in the following journal.
Name: Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22233540
- DOI: http://dx.doi.org/10.3109/14756366.2011.640632
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