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Pentepeptide
Repeat Protein MfpA from Mycobacterium tuberculosis
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A
fluoroquinolone resistance protein from Mycobacterium
tuberculosis that mimics DNA.
Science
(2005).
308(5727):1480-3.
Comments on:
Science.
(2005) 308(5727):1480-3.
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Principle
Investigator:
John Blanchard
Research:
Matt Vetting
Subray Hegde
Collaborators:
Steven Roderick
Lesley
Mitchenall
Tony Maxwell
Howard Takiff
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PDB DATABASE
IDENTIFIERS
2BM4,
2BM5,
2BM6,
2BM7
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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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