A Fluoroquinolone Resistance Protein from Mycobacterium tuberculosis That Mimics DNA-Reference-Cited by-同舟云学术

A Fluoroquinolone Resistance Protein from Mycobacterium tuberculosis That Mimics DNA

Published:2005-06-03 Issue:5727 Volume:308 Page:1480-1483
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Hegde Subray S.¹²³,Vetting Matthew W.¹²³,Roderick Steven L.¹²³,Mitchenall Lesley A.¹²³,Maxwell Anthony¹²³,Takiff Howard E.¹²³,Blanchard John S.¹²³

Affiliation:

1. Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.

2. Department of Biological Chemistry, John Innes Centre, Colney Lane, Norwich NR4 7UH, UK.

3. Laboratorio de Genética Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas 1020A, Venezuela.

Abstract

Fluoroquinolones are gaining increasing importance in the treatment of tuberculosis. The expression of MfpA, a member of the pentapeptide repeat family of proteins from Mycobacterium tuberculosis , causes resistance to ciprofloxacin and sparfloxacin. This protein binds to DNA gyrase and inhibits its activity. Its three-dimensional structure reveals a fold, which we have named the right-handed quadrilateral β helix, that exhibits size, shape, and electrostatic similarity to B-form DNA. This represents a form of DNA mimicry and explains both its inhibitory effect on DNA gyrase and fluoroquinolone resistance resulting from the protein's expression in vivo.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference33 articles.

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