Imidazole Antibiotics Inhibit the Nitric Oxide Dioxygenase Function of Microbial Flavohemoglobin
| Autor: | Anne M. Gardner, Paul R. Gardner, Arin E. Fletcher, Angela N. Hvitved, Ryan A. Helmick, Christopher R. Gessner, Michael C. Gustin |
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| Rok vydání: | 2005 |
| Předmět: |
Hemeproteins
Econazole Heme Nitric Oxide Nitric oxide Microbiology chemistry.chemical_compound Dihydropteridine Reductase Candida albicans Escherichia coli medicine NADH NADPH Oxidoreductases Pharmacology (medical) Enzyme Inhibitors Mechanisms of Action: Physiological Effects Antibacterial agent Pharmacology biology Escherichia coli Proteins Imidazoles Nitric oxide dioxygenase NAD biology.organism_classification Anti-Bacterial Agents Kinetics Infectious Diseases chemistry Biochemistry Flavin-Adenine Dinucleotide Oxygenases Growth inhibition Uncompetitive inhibitor Oxidation-Reduction Bacteria Plasmids medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 49:1837-1843 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.49.5.1837-1843.2005 |
| Popis: | Flavohemoglobins metabolize nitric oxide (NO) to nitrate and protect bacteria and fungi from NO-mediated damage, growth inhibition, and killing by NO-releasing immune cells. Antimicrobial imidazoles were tested for their ability to coordinate flavohemoglobin and inhibit its NO dioxygenase (NOD) function. Miconazole, econazole, clotrimazole, and ketoconazole inhibited the NOD activity of Escherichia coli flavohemoglobin with apparent K i values of 80, 550, 1,300, and 5,000 nM, respectively. Saccharomyces cerevisiae , Candida albicans , and Alcaligenes eutrophus enzymes exhibited similar sensitivities to imidazoles. Imidazoles coordinated the heme iron atom, impaired ferric heme reduction, produced uncompetitive inhibition with respect to O 2 and NO, and inhibited NO metabolism by yeasts and bacteria. Nevertheless, these imidazoles were not sufficiently selective to fully mimic the NO-dependent growth stasis seen with NOD-deficient mutants. The results demonstrate a mechanism for NOD inhibition by imidazoles and suggest a target for imidazole engineering. |
| Databáze: | OpenAIRE |
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