Structural highlights
3m4i is a 1 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | |
| Related: | 3ig0, 3ifz, 2zjt |
| Gene: | gyrB, MT0005, MTCY10H4.03, Rv0005 ("Bacillus tuberculosis" (Zopf 1883) Klein 1884) |
| Activity: | DNA topoisomerase (ATP-hydrolyzing), with EC number 5.99.1.3 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[GYRB_MYCTU] 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).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechanism, which emerges in extensively drug resistant tuberculosis, we performed combined functional, biophysical and structural studies of the two individual domains constituting the catalytic DNA gyrase reaction core, namely the Toprim and the breakage-reunion domains. This allowed us to produce a model of the catalytic reaction core in complex with DNA and a quinolone molecule, identifying original mechanistic properties of quinolone binding and clarifying the relationships between amino acid mutations and resistance phenotype of M. tuberculosis DNA gyrase. These results are compatible with our previous studies on quinolone resistance. Interestingly, the structure of the entire breakage-reunion domain revealed a new interaction, in which the Quinolone-Binding Pocket (QBP) is blocked by the N-terminal helix of a symmetry-related molecule. This interaction provides useful starting points for designing peptide based inhibitors that target DNA gyrase to prevent its binding to DNA.
Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyrase.,Piton J, Petrella S, Delarue M, Andre-Leroux G, Jarlier V, Aubry A, Mayer C PLoS One. 2010 Aug 18;5(8):e12245. PMID:20805881[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Piton J, Petrella S, Delarue M, Andre-Leroux G, Jarlier V, Aubry A, Mayer C. Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyrase. PLoS One. 2010 Aug 18;5(8):e12245. PMID:20805881 doi:10.1371/journal.pone.0012245
