Rox, a Rifamycin Resistance Enzyme with an Unprecedented Mechanism of Action.
Cell Chem Biol
; 25(4): 403-412.e5, 2018 04 19.
Article
em En
| MEDLINE
| ID: mdl-29398560
Rifamycin monooxygenases (Rox) are present in a variety of environmental bacteria and are associated with decomposition of the clinically utilized antibiotic rifampin. Here we report the structure and function of a drug-inducible rox gene from Streptomyces venezuelae, which encodes a class A flavoprotein monooxygenase that inactivates a broad range of rifamycin antibiotics. Our findings describe a mechanism of rifamycin inactivation initiated by monooxygenation of the 2-position of the naphthyl group, which subsequently results in ring opening and linearization of the antibiotic. The result is an antibiotic that no longer adopts the basket-like structure essential for binding to the RNA exit tunnel of the target RpoB, thereby providing the molecular logic of resistance. This unique mechanism of enzymatic inactivation underpins the broad spectrum of rifamycin resistance mediated by Rox enzymes and presents a new antibiotic resistance mechanism not yet seen in microbial antibiotic detoxification.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rifamicinas
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Streptomyces
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Proteínas de Bactérias
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Farmacorresistência Bacteriana
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Oxigenases de Função Mista
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Antibacterianos
Idioma:
En
Revista:
Cell Chem Biol
Ano de publicação:
2018
Tipo de documento:
Article