Biochemistry: A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA

被引:207
作者
机构
[1] Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461
[2] Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, Colney Lane
[3] Laboratorio de Genética Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas
关键词
Antibiotics - Bacteria - Disease control - DNA - Enzyme inhibition - Enzyme kinetics - Polypeptides;
D O I
10.1126/science.1110699
中图分类号
学科分类号
摘要
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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页码:1480 / 1483
页数:3
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