Structural highlights
4tma is a 12 chain structure with sequence from Ecoli and Escherichia coli str. k-12 substr. mc4100. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | |
| Gene: | gyrA, BN896_2003 (Escherichia coli str. K-12 substr. MC4100), gyrB, BN896_3389 (Escherichia coli str. K-12 substr. MC4100), yacG, b0101, JW5008 (ECOLI) |
| Activity: | DNA topoisomerase (ATP-hydrolyzing), with EC number 5.99.1.3 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[U6NB78_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 (By similarity).[HAMAP-Rule:MF_01897] [YACG_ECOLI] Inhibits all the catalytic activities of DNA gyrase by preventing its interaction with DNA. Acts by binding directly to the C-terminal domain of GyrB, which probably disrupts DNA binding by the gyrase.[1] [U6NGU8_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 (By similarity).[HAMAP-Rule:MF_01898]
Publication Abstract from PubMed
Precise control of supercoiling homeostasis is critical to DNA-dependent processes such as gene expression, replication, and damage response. Topoisomerases are central regulators of DNA supercoiling commonly thought to act independently in the recognition and modulation of chromosome superstructure; however, recent evidence has indicated that cells tightly regulate topoisomerase activity to support chromosome dynamics, transcriptional response, and replicative events. How topoisomerase control is executed and linked to the internal status of a cell is poorly understood. To investigate these connections, we determined the structure of Escherichia coli gyrase, a type IIA topoisomerase bound to YacG, a recently identified chromosomally encoded inhibitor protein. Phylogenetic analyses indicate that YacG is frequently associated with coenzyme A (CoA) production enzymes, linking the protein to metabolism and stress. The structure, along with supporting solution studies, shows that YacG represses gyrase by sterically occluding the principal DNA-binding site of the enzyme. Unexpectedly, YacG acts by both engaging two spatially segregated regions associated with small-molecule inhibitor interactions (fluoroquinolone antibiotics and the newly reported antagonist GSK299423) and remodeling the gyrase holoenzyme into an inactive, ATP-trapped configuration. This study establishes a new mechanism for the protein-based control of topoisomerases, an approach that may be used to alter supercoiling levels for responding to changes in cellular state.
Direct control of type IIA topoisomerase activity by a chromosomally encoded regulatory protein.,Vos SM, Lyubimov AY, Hershey DM, Schoeffler AJ, Sengupta S, Nagaraja V, Berger JM Genes Dev. 2014 Jul 1;28(13):1485-97. doi: 10.1101/gad.241984.114. PMID:24990966[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sengupta S, Nagaraja V. YacG from Escherichia coli is a specific endogenous inhibitor of DNA gyrase. Nucleic Acids Res. 2008 Aug;36(13):4310-6. doi: 10.1093/nar/gkn355. Epub 2008 Jun, 27. PMID:18586829 doi:http://dx.doi.org/10.1093/nar/gkn355
- ↑ Vos SM, Lyubimov AY, Hershey DM, Schoeffler AJ, Sengupta S, Nagaraja V, Berger JM. Direct control of type IIA topoisomerase activity by a chromosomally encoded regulatory protein. Genes Dev. 2014 Jul 1;28(13):1485-97. doi: 10.1101/gad.241984.114. PMID:24990966 doi:http://dx.doi.org/10.1101/gad.241984.114
