2y3p
Crystal structure of N-terminal domain of GyrA with the antibiotic simocyclinone D8Crystal structure of N-terminal domain of GyrA with the antibiotic simocyclinone D8
Structural highlights
FunctionGYRA_SHIFL DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings (By similarity). Publication Abstract from PubMedSimocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme. We report the crystal structure of the complex formed between the N-terminal domain of the Escherichia coli gyrase A subunit and simocyclinone D8, revealing two binding pockets that separately accommodate the aminocoumarin and polyketide moieties of the antibiotic. These are close to, but distinct from, the quinolone-binding site, consistent with our observations that several mutations in this region confer resistance to both agents. Biochemical studies show that the individual moieties of simocyclinone D8 are comparatively weak inhibitors of gyrase relative to the parent compound, but their combination generates a more potent inhibitor. Our results should facilitate the design of drug molecules that target these unexploited binding pockets. A crystal structure of the bifunctional antibiotic simocyclinone D8, bound to DNA gyrase.,Edwards MJ, Flatman RH, Mitchenall LA, Stevenson CE, Le TB, Clarke TA, McKay AR, Fiedler HP, Buttner MJ, Lawson DM, Maxwell A Science. 2009 Dec 4;326(5958):1415-8. PMID:19965760[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||