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A Fluoroquinolone Resistance Protein from Mycobacterium tuberculosis That Mimics DNA
Subray S. Hegde,1*Matthew W. Vetting,1*Steven L. Roderick,1Lesley A. Mitchenall,2Anthony Maxwell,2Howard E. Takiff,3John S. Blanchard1
Fluoroquinolones are gaining increasing importance in the treatmentof tuberculosis. The expression of MfpA, a member of the pentapeptiderepeat family of proteins from Mycobacterium tuberculosis, causesresistance to ciprofloxacin and sparfloxacin. This protein bindsto DNA gyrase and inhibits its activity. Its three-dimensionalstructure reveals a fold, which we have named the right-handedquadrilateral ß helix, that exhibits size, shape,and electrostatic similarity to B-form DNA. This representsa form of DNA mimicry and explains both its inhibitory effecton DNA gyrase and fluoroquinolone resistance resulting fromthe protein's expression in vivo.
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.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: blanchar{at}aecom.yu.edu
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