Your browser doesn't support javascript.
loading
Baeyer-Villiger Monooxygenases EthA and MymA Are Required for Activation of Replicating and Non-replicating Mycobacterium tuberculosis Inhibitors.
Grant, Sarah Schmidt; Wellington, Samantha; Kawate, Tomohiko; Desjardins, Christopher A; Silvis, Melanie R; Wivagg, Carl; Thompson, Matthew; Gordon, Katherine; Kazyanskaya, Edward; Nietupski, Raymond; Haseley, Nathan; Iwase, Noriaki; Earl, Ashlee M; Fitzgerald, Michael; Hung, Deborah T.
Afiliação
  • Grant SS; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Center for Computational and Integrative Biology, Massachusetts General Hospit
  • Wellington S; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Kawate T; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Molecular Biology, Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Desjardins CA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Silvis MR; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Wivagg C; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Thompson M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Gordon K; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Kazyanskaya E; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Nietupski R; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Haseley N; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Iwase N; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Earl AM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Fitzgerald M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Hung DT; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Molecular Biology, Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Electro
Cell Chem Biol ; 23(6): 666-77, 2016 06 23.
Article em En | MEDLINE | ID: mdl-27321573
ABSTRACT
Successful treatment of Mycobacterium tuberculosis infection typically requires a complex regimen administered over at least 6 months. Interestingly, many of the antibiotics used to treat M. tuberculosis are prodrugs that require intracellular activation. Here, we describe three small molecules, active against both replicating and non-replicating M. tuberculosis, that require activation by Baeyer-Villiger monooxygenases (BVMOs). Two molecules require BVMO EthA (Rv3854c) for activation and the third molecule requires the BVMO MymA (Rv3083). While EthA is known to activate the antitubercular drug ethionamide, this is the first description of MymA as an activating enzyme of a prodrug. Furthermore, we found that MymA also plays a role in activating ethionamide, with loss of MymA function resulting in ethionamide-resistant M. tuberculosis. These findings suggest overlap in function and specificity of the BVMOs in M. tuberculosis.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 / 3_ND Base de dados: MEDLINE Assunto principal: Oxirredutases / Etionamida / Bibliotecas de Moléculas Pequenas / Oxigenases de Função Mista / Mycobacterium tuberculosis / Antituberculosos Idioma: En Revista: Cell Chem Biol Ano de publicação: 2016 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 / 3_ND Base de dados: MEDLINE Assunto principal: Oxirredutases / Etionamida / Bibliotecas de Moléculas Pequenas / Oxigenases de Função Mista / Mycobacterium tuberculosis / Antituberculosos Idioma: En Revista: Cell Chem Biol Ano de publicação: 2016 Tipo de documento: Article