7c7n

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Crystal structure of E.coli DNA gyrase B in complex with 6-fluoro-8-(methylamino)-2-oxo-1,2-dihydroquinoline derivativeCrystal structure of E.coli DNA gyrase B in complex with 6-fluoro-8-(methylamino)-2-oxo-1,2-dihydroquinoline derivative

Structural highlights

7c7n is a 1 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GYRB_ECOLI 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.[1] [2] [3]

Publication Abstract from PubMed

The global increase in multidrug-resistant pathogens has caused severe problems in the treatment of infections. To overcome these difficulties, the advent of a new chemical class of antibacterial drug is eagerly desired. We aimed at creating novel antibacterial agents against bacterial type II topoisomerases, which are well-validated targets. TP0480066 (compound 32) has been identified by using structure-based optimization originated from lead compound 1, which was obtained as a result of our previous lead identification studies. The MIC90 values of TP0480066 against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and genotype penicillin-resistant Streptococcus pneumoniae (gPRSP) were 0.25, 0.015, and 0.06 mug/mL, respectively. Hence, TP0480066 can be regarded as a promising antibacterial drug candidate of this chemical class.

Lead optimization of 8-(methylamino)-2-oxo-1,2-dihydroquinolines as bacterial type II topoisomerase inhibitors.,Ushiyama F, Amada H, Mihara Y, Takeuchi T, Tanaka-Yamamoto N, Mima M, Kamitani M, Wada R, Tamura Y, Endo M, Masuko A, Takata I, Hitaka K, Sugiyama H, Ohtake N Bioorg Med Chem. 2020 Sep 22;28(22):115776. doi: 10.1016/j.bmc.2020.115776. PMID:33032189[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Noble CG, Maxwell A. The role of GyrB in the DNA cleavage-religation reaction of DNA gyrase: a proposed two metal-ion mechanism. J Mol Biol. 2002 Apr 26;318(2):361-71. PMID:12051843 doi:http://dx.doi.org/10.1016/S0022-2836(02)00049-9
  2. ↑ Sissi C, Chemello A, Vazquez E, Mitchenall LA, Maxwell A, Palumbo M. DNA gyrase requires DNA for effective two-site coordination of divalent metal ions: further insight into the mechanism of enzyme action. Biochemistry. 2008 Aug 19;47(33):8538-45. doi: 10.1021/bi800480j. Epub 2008 Jul, 22. PMID:18642932 doi:http://dx.doi.org/10.1021/bi800480j
  3. ↑ Schoeffler AJ, May AP, Berger JM. A domain insertion in Escherichia coli GyrB adopts a novel fold that plays a critical role in gyrase function. Nucleic Acids Res. 2010 Jul 31. PMID:20675723 doi:10.1093/nar/gkq665
  4. ↑ Ushiyama F, Amada H, Mihara Y, Takeuchi T, Tanaka-Yamamoto N, Mima M, Kamitani M, Wada R, Tamura Y, Endo M, Masuko A, Takata I, Hitaka K, Sugiyama H, Ohtake N. Lead optimization of 8-(methylamino)-2-oxo-1,2-dihydroquinolines as bacterial type II topoisomerase inhibitors. Bioorg Med Chem. 2020 Sep 22;28(22):115776. doi: 10.1016/j.bmc.2020.115776. PMID:33032189 doi:http://dx.doi.org/10.1016/j.bmc.2020.115776

7c7n, resolution 2.30Å

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