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4fm9

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==Human topoisomerase II alpha bound to DNA==
==Human topoisomerase II alpha bound to DNA==
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<StructureSection load='4fm9' size='340' side='right' caption='[[4fm9]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
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<StructureSection load='4fm9' size='340' side='right'caption='[[4fm9]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4fm9]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FM9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FM9 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4fm9]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FM9 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.901&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TOP2, TOP2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_topoisomerase_(ATP-hydrolyzing) DNA topoisomerase (ATP-hydrolyzing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.3 5.99.1.3] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4fm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fm9 OCA], [https://pdbe.org/4fm9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fm9 RCSB], [https://www.ebi.ac.uk/pdbsum/4fm9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fm9 ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4fm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fm9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fm9 RCSB], [http://www.ebi.ac.uk/pdbsum/4fm9 PDBsum]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/TOP2A_HUMAN TOP2A_HUMAN]] 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.<ref>PMID:22323612</ref>
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[https://www.uniprot.org/uniprot/TOP2A_HUMAN TOP2A_HUMAN] 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.<ref>PMID:22323612</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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-A-resolution structure of the DNA cleavage core of human topoisomerase IIalpha (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 IIbeta (TOP2B) suggests possible modification points for developing paralog-specific inhibitors to overcome the tendency of topoisomerase II-targeting chemotherapeutics to generate secondary malignancies.
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The Structure of DNA-Bound Human Topoisomerase II Alpha: Conformational Mechanisms for Coordinating Inter-Subunit Interactions with DNA Cleavage.,Wendorff TJ, Schmidt BH, Heslop P, Austin CA, Berger JM J Mol Biol. 2012 Dec 7;424(3-4):109-24. doi: 10.1016/j.jmb.2012.07.014. Epub 2012, Jul 25. PMID:22841979<ref>PMID:22841979</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[Topoisomerase|Topoisomerase]]
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*[[Topoisomerase 3D structures|Topoisomerase 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Austin, C A]]
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[[Category: Large Structures]]
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[[Category: Berger, J M]]
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[[Category: Synthetic construct]]
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[[Category: Heslop, P]]
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[[Category: Austin CA]]
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[[Category: Schmidt, B H]]
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[[Category: Berger JM]]
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[[Category: Wendorff, T J]]
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[[Category: Heslop P]]
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[[Category: Dna-binding]]
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[[Category: Schmidt BH]]
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[[Category: Isomerase-dna complex]]
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[[Category: Wendorff TJ]]
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[[Category: Protein-dna complex]]
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[[Category: Topoisomerase]]
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Current revision

Human topoisomerase II alpha bound to DNA

PDB ID 4fm9

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