Biochemistry

A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA

Subray Hegde, Matthew W. Vetting, Steven L. Roderick, Lesley A. Mitchenall, Anthony Maxwell, Howard E. Takiff, John S. Blanchard

Research output: Contribution to journalArticle

181 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1480-1483
Number of pages4
JournalScience
Volume308
Issue number5727
DOIs
StatePublished - Jun 3 2005

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Fluoroquinolones
Mycobacterium tuberculosis
Biochemistry
DNA Gyrase
DNA
B-Form DNA
Molecular Mimicry
Proteins
Ciprofloxacin
Static Electricity
Tuberculosis

ASJC Scopus subject areas

  • General

Cite this

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

In: Science, Vol. 308, No. 5727, 03.06.2005, p. 1480-1483.

Research output: Contribution to journalArticle

Hegde, S, Vetting, MW, Roderick, SL, Mitchenall, LA, Maxwell, A, Takiff, HE & Blanchard, JS 2005, 'Biochemistry: A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA', Science, vol. 308, no. 5727, pp. 1480-1483. https://doi.org/10.1126/science.1110699
Hegde S, Vetting MW, Roderick SL, Mitchenall LA, Maxwell A, Takiff HE et al. Biochemistry: A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science. 2005 Jun 3;308(5727):1480-1483. https://doi.org/10.1126/science.1110699
Hegde, Subray ; Vetting, Matthew W. ; Roderick, Steven L. ; Mitchenall, Lesley A. ; Maxwell, Anthony ; Takiff, Howard E. ; Blanchard, John S. / Biochemistry : A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. In: Science. 2005 ; Vol. 308, No. 5727. pp. 1480-1483.
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