| http://purl.uniprot.org/citations/22841979 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22841979 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22841979 | http://www.w3.org/2000/01/rdf-schema#comment | "Type II topoisomerases are required for the management of DNA superhelicity and chromosome segregation, and serve as frontline targets for a variety of small-molecule therapeutics. To better understand how these enzymes act in both contexts, we determined the 2.9-Å-resolution structure of the DNA cleavage core of human topoisomerase IIα (TOP2A) bound to a doubly nicked, 30-bp duplex oligonucleotide. In accord with prior biochemical and structural studies, TOP2A significantly bends its DNA substrate using a bipartite, nucleolytic center formed at an N-terminal dimerization interface of the cleavage core. However, the protein also adopts a global conformation in which the second of its two inter-protomer contact points, one at the C-terminus, has separated. This finding, together with comparative structural analyses, reveals that the principal site of DNA engagement undergoes highly quantized conformational transitions between distinct binding, cleavage, and drug-inhibited states that correlate with the control of subunit-subunit interactions. Additional consideration of our TOP2A model in light of an etoposide-inhibited complex of human topoisomerase IIβ (TOP2B) suggests possible modification points for developing paralog-specific inhibitors to overcome the tendency of topoisomerase II-targeting chemotherapeutics to generate secondary malignancies."xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2012.07.014"xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2012.07.014"xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/author | "Berger J.M."xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/author | "Berger J.M."xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/author | "Heslop P."xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/author | "Heslop P."xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/author | "Schmidt B.H."xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/author | "Schmidt B.H."xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/author | "Austin C.A."xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/author | "Austin C.A."xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/author | "Wendorff T.J."xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/author | "Wendorff T.J."xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/name | "J. Mol. Biol."xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/name | "J. Mol. Biol."xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/pages | "109-124"xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/pages | "109-124"xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/title | "The structure of DNA-bound human topoisomerase II alpha: conformational mechanisms for coordinating inter-subunit interactions with DNA cleavage."xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/title | "The structure of DNA-bound human topoisomerase II alpha: conformational mechanisms for coordinating inter-subunit interactions with DNA cleavage."xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/volume | "424"xsd:string |
| http://purl.uniprot.org/citations/22841979 | http://purl.uniprot.org/core/volume | "424"xsd:string |