Benzothiazinones: prodrugs that covalently modify the decaprenylphosphoryl-β-D-ribose 2'-epimerase DprE1 of Mycobacterium tuberculosis
| Autor: | Patricia Schneider, Marlon J. Hinner, Makarov Vadim A, Claudia Trefzer, Monica Rengifo-Gonzalez, Kai Johnsson, Stewart T. Cole |
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| Rok vydání: | 2010 |
| Předmět: |
Stereochemistry
Molecular Conformation Racemases and Epimerases Thiazines Biochemistry Catalysis Mycobacterium tuberculosis chemistry.chemical_compound Residue (chemistry) Structure-Activity Relationship Colloid and Surface Chemistry Catalytic Domain Ribose medicine Prodrugs biology Active site Stereoisomerism General Chemistry Nitroso Prodrug biology.organism_classification Anti-Bacterial Agents chemistry Mechanism of action biology.protein medicine.symptom Cysteine |
| Zdroj: | Journal of the American Chemical Society. 132(39) |
| ISSN: | 1520-5126 |
| Popis: | Benzothiazinones (BTZs) form a new class of potent antimycobacterial agents. Although the target of BTZs has been identified as decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1), their detailed mechanism of action remains obscure. Here we demonstrate that BTZs are activated in the bacterium by reduction of an essential nitro group to a nitroso derivative, which then specifically reacts with a cysteine residue in the active site of DprE1. |
| Databáze: | OpenAIRE |
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