A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA.
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.
Hegde
Subray S
SS
Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Vetting
Matthew W
MW
Roderick
Steven L
SL
Mitchenall
Lesley A
LA
Maxwell
Anthony
A
Takiff
Howard E
HE
Blanchard
John S
JS
D000595:Amino Acid Sequence; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology*; D002939:Ciprofloxacin / Q000494:pharmacology; D018360:Crystallography, X-Ray; D027081:DNA Gyrase / Q000378:metabolism; D004269:DNA, Bacterial / Q000737:chemistry*; D004278:DNA, Superhelical / Q000737:chemistry; D024881:Drug Resistance, Bacterial; D004352:Drug Resistance, Microbial / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000737:chemistry; D004926:Escherichia coli / Q000201:enzymology; D024841:Fluoroquinolones / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000502:physiology*; D011487:Protein Conformation; D017510:Protein Folding; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D059005:Topoisomerase II Inhibitors; D002939:Ciprofloxacin; C445685:MfpA protein, Mycobacterium smegmatis; D020559:Monomeric GTP-Binding Proteins; D027081:DNA Gyrase; C061363:sparfloxacin