Insights into Tuberculosis Drug Resistance

Science  03 Jun 2005:
Vol. 308, Issue 5727, pp. 1373
DOI: 10.1126/science.308.5727.1373k

Fluoroquinolone antibiotics are increasingly being used in the treatment of tuberculosis. They act by inhibiting DNA gyrase through binding to the enzyme-DNA complex in Mycobacterium tuberculosis. Genetic selection in M. smegmatis identified a protein, MFpA, that confers resistance to fluoroquinolones. Hegde et al. (p. 1480; see the news story by Ferber) have determined the structure of MfpA from M. tuberculosis to 2.0 angstrom resolution. It adopts a fold, the right-handed quadrilateral β-helix, that mimics double-helical DNA in size, shape, and charge distribution so that the protein competes with DNA for binding to DNA gyrase.

Related Content

Navigate This Article