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A Fluoroquinolone Resistance Protein from Mycobacterium tuberculosis That Mimics DNA

Science  03 Jun 2005:
Vol. 308, Issue 5727, pp. 1480-1483
DOI: 10.1126/science.1110699

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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.

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