Structural highlights
Function
[GYRB_THET8] A type II topoisomerase that negatively supercoils closed circular double-stranded (ds) DNA in an ATP-dependent manner (PubMed:23804759, PubMed:11850422). It probably also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes (PubMed:11850422). Relaxes negatively supercoiled DNA in an ATP-independent manner (PubMed:23804759, PubMed:11850422). At comparable concentrations T.thermophilus gyrase does not introduce as many negative supercoils into DNA as the E.coli enzyme (PubMed:23804759).[1] Negative supercoiling favors strand separation, and DNA replication, transcription, recombination and repair, all of which involve strand separation. Type II topoisomerases break and join 2 DNA strands simultaneously in an ATP-dependent manner.
Publication Abstract from PubMed
Coumermycin A1 is a natural aminocoumarin that inhibits bacterial DNA gyrase, a member of the GHKL proteins superfamily. We report here the first cocrystal structures of gyrase B bound to coumermycin A1, revealing that one coumermycin A1 molecule traps simultaneously two ATP-binding sites. The inhibited dimers from different species adopt distinct sequence-dependent conformations, alternative to the ATP-bound form. These structures provide a basis for the rational development of coumermycin A1 derivatives for antibiotherapy and biotechnology applications.
Structural Basis for DNA Gyrase Interaction with Coumermycin A1.,Vanden Broeck A, McEwen AG, Chebaro Y, Potier N, Lamour V J Med Chem. 2019 Apr 3. doi: 10.1021/acs.jmedchem.8b01928. PMID:30920824[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Papillon J, Menetret JF, Batisse C, Helye R, Schultz P, Potier N, Lamour V. Structural insight into negative DNA supercoiling by DNA gyrase, a bacterial type 2A DNA topoisomerase. Nucleic Acids Res. 2013 Sep;41(16):7815-27. doi: 10.1093/nar/gkt560. Epub 2013, Jun 26. PMID:23804759 doi:http://dx.doi.org/10.1093/nar/gkt560
- ↑ Vanden Broeck A, McEwen AG, Chebaro Y, Potier N, Lamour V. Structural Basis for DNA Gyrase Interaction with Coumermycin A1. J Med Chem. 2019 Apr 3. doi: 10.1021/acs.jmedchem.8b01928. PMID:30920824 doi:http://dx.doi.org/10.1021/acs.jmedchem.8b01928
