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. 2005 Jun 3;308(5727):1480-3.
doi: 10.1126/science.1110699.

A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA

Subray S Hegde  1 , Matthew W Vetting, Steven L Roderick, Lesley A Mitchenall, Anthony Maxwell, Howard E Takiff, John S Blanchard
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A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA

Subray S Hegde et al. Science. .

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 beta 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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