Structural highlights
Function
[TOP2_YEAST] Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes.[1] [2]
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
Type II topoisomerases disentangle DNA to facilitate chromosome segregation, and represent a major class of therapeutic targets. Although these enzymes have been studied extensively, a molecular understanding of DNA binding has been lacking. Here we present the structure of a complex between the DNA-binding and cleavage core of Saccharomyces cerevisiae Topo II (also known as Top2) and a gate-DNA segment. The structure reveals that the enzyme enforces a 150 degrees DNA bend through a mechanism similar to that of remodelling proteins such as integration host factor. Large protein conformational changes accompany DNA deformation, creating a bipartite catalytic site that positions the DNA backbone near a reactive tyrosine and a coordinated magnesium ion. This configuration closely resembles the catalytic site of type IA topoisomerases, reinforcing an evolutionary link between these structurally and functionally distinct enzymes. Binding of DNA facilitates opening of an enzyme dimerization interface, providing visual evidence for a key step in DNA transport.
Structural basis for gate-DNA recognition and bending by type IIA topoisomerases.,Dong KC, Berger JM Nature. 2007 Dec 20;450(7173):1201-5. PMID:18097402[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu Q, Wang JC. Identification of active site residues in the "GyrA" half of yeast DNA topoisomerase II. J Biol Chem. 1998 Aug 7;273(32):20252-60. PMID:9685374
- ↑ Schmidt BH, Osheroff N, Berger JM. Structure of a topoisomerase II-DNA-nucleotide complex reveals a new control mechanism for ATPase activity. Nat Struct Mol Biol. 2012 Nov;19(11):1147-54. doi: 10.1038/nsmb.2388. Epub 2012, Sep 30. PMID:23022727 doi:http://dx.doi.org/10.1038/nsmb.2388
- ↑ Dong KC, Berger JM. Structural basis for gate-DNA recognition and bending by type IIA topoisomerases. Nature. 2007 Dec 20;450(7173):1201-5. PMID:18097402 doi:10.1038/nature06396
