Inhibition of metallo-beta-lactamases by a series of thiol ester derivatives of mercaptophenylacetic acid
| Autor: | Stewart C. Pearson, David Proctor, Robert Reid, Teresa Khushi, Bateson John Hargreaves, David J. Payne, Brian Charles Gasson |
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| Rok vydání: | 1998 |
| Předmět: |
Stereochemistry
Carboxylic acid Bacillus cereus Substituent Microbiology beta-Lactamases Substrate Specificity chemistry.chemical_compound Metalloproteins Genetics Organic chemistry Chelation Sulfhydryl Compounds Molecular Biology chemistry.chemical_classification Binding Sites biology Chemistry Active site Isothermal titration calorimetry Esters biology.organism_classification enzymes and coenzymes (carbohydrates) Zinc Enzyme Thiol biology.protein bacteria beta-Lactamase Inhibitors |
| Zdroj: | FEMS microbiology letters. 157(1) |
| ISSN: | 0378-1097 |
| Popis: | A series of mercaptophenylacetic acid thiol esters bearing a phenyl substituent adjacent to the carboxylic acid function has been shown to be inhibitors of metallo-beta-lactamases. The inhibition of the Bacteroides fragilis CfiA and Bacillus cereus II metallo-beta-lactamases was Zn2- dependent, greater inhibition being observed at 1 microM ZnSO4 than at 100 microM ZnSO4. Despite this Zn2+ dependency, isothermal titration calorimetry studies illustrated that representative compounds had no detectable affinity for Zn2+ (K1 mM). This indicates that their mode of inhibition was not by chelation of the active site Zn2+. Greatest potency was observed against the Stenotrophomonas maltophilia L1 metallo-beta-lactamase with I50 values of between1.95 microM and 6 microM and SB-217843 exhibited a similar level of inhibition of this enzyme at 1 and 100 microM Zn2+ (I50 values 5 and 6 microM, respectively). Inhibition of B. cereus II metallo-beta-lactamase by SB-218018 and SB-217782 was competitive with Ki values of 185 microM and 1500 microM, respectively. Therefore, these compounds are specific inhibitors of metallo-beta-lactamases and provide further probes of the active sites of these enzymes. |
| Databáze: | OpenAIRE |
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