2Y3P

Crystal structure of N-terminal domain of GyrA with the antibiotic simocyclinone D8

Replaces:  2WL2

Summary for 2Y3P

• Entry DOI: 10.2210/pdb2y3p/pdb
• Descriptor: DNA GYRASE SUBUNIT A, MAGNESIUM ION, SIMOCYCLINONE D8, ... (4 entities in total)
• Functional Keywords: isomerase, aminocoumarin antibiotic
• Biological source: ESCHERICHIA COLI
• Cellular location: Cytoplasm : P0AES5
• Total number of polymer chains: 2
• Total formula weight: 119207.82

Authors

Edwards, M.J.,Flatman, R.H.,Mitchenall, L.A.,Stevenson, C.E.M.,Le, T.B.K.,Clarke, T.A.,McKay, A.R.,Fiedler, H.-P.,Buttner, M.J.,Lawson, D.M.,Maxwell, A. (deposition date: 2010-12-22, release date: 2010-12-29, Last modification date: 2023-12-20)

Primary citation

Edwards, M.J.,Flatman, R.H.,Mitchenall, L.A.,Stevenson, C.E.M.,Le, T.B.K.,Clarke, T.A.,Mckay, A.R.,Fiedler, H.-P.,Buttner, M.J.,Lawson, D.M.,Maxwell, A.
A Crystal Structure of the Bifunctional Antibiotic Simocyclinone D8, Bound to DNA Gyrase.
Science, 326:1415-, 2009

PubMed Abstract: Simocyclinones 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.

PubMed: 19965760
DOI: 10.1126/SCIENCE.1179123

Experimental method

X-RAY DIFFRACTION (2.62 Å)