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| | ==Crystal structure of human topoisomerase II beta in complex with DNA: a new quaternary conformation showing opening of the protein-linked DNA-gate== | | ==Crystal structure of human topoisomerase II beta in complex with DNA: a new quaternary conformation showing opening of the protein-linked DNA-gate== |
| - | <StructureSection load='5zen' size='340' side='right' caption='[[5zen]], [[Resolution|resolution]] 2.75Å' scene=''> | + | <StructureSection load='5zen' size='340' side='right'caption='[[5zen]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5zen]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZEN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZEN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5zen]] 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=5ZEN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZEN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TOP2B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> |
| - | <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> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5zen FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zen OCA], [https://pdbe.org/5zen PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zen RCSB], [https://www.ebi.ac.uk/pdbsum/5zen PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zen ProSAT]</span></td></tr> |
| - | <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=5zen FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zen OCA], [http://pdbe.org/5zen PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zen RCSB], [http://www.ebi.ac.uk/pdbsum/5zen PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zen ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TOP2B_HUMAN TOP2B_HUMAN]] Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Indirectly involved in vitamin D-coupled transcription regulation via its association with the WINAC complex, a chromatin-remodeling complex recruited by vitamin D receptor (VDR), which is required for the ligand-bound VDR-mediated transrepression of the CYP27B1 gene.<ref>PMID:10684600</ref> <ref>PMID:12837248</ref> | + | [https://www.uniprot.org/uniprot/TOP2B_HUMAN TOP2B_HUMAN] Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Indirectly involved in vitamin D-coupled transcription regulation via its association with the WINAC complex, a chromatin-remodeling complex recruited by vitamin D receptor (VDR), which is required for the ligand-bound VDR-mediated transrepression of the CYP27B1 gene.<ref>PMID:10684600</ref> <ref>PMID:12837248</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5zen" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5zen" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Topoisomerase 3D structures|Topoisomerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Chan, N L]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, S F]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Wang, Y R]] | + | [[Category: Chan NL]] |
| - | [[Category: Cleavage complex]] | + | [[Category: Chen SF]] |
| - | [[Category: Dna-gate]] | + | [[Category: Wang YR]] |
| - | [[Category: Isomerase-dna complex]]
| + | |
| - | [[Category: Type ii topoisomerase]]
| + | |
| Structural highlights
Function
TOP2B_HUMAN Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Indirectly involved in vitamin D-coupled transcription regulation via its association with the WINAC complex, a chromatin-remodeling complex recruited by vitamin D receptor (VDR), which is required for the ligand-bound VDR-mediated transrepression of the CYP27B1 gene.[1] [2]
Publication Abstract from PubMed
Type IIA topoisomerases (Top2s) manipulate the handedness of DNA crossovers by introducing a transient and protein-linked double-strand break in one DNA duplex, termed the DNA-gate, whose opening allows another DNA segment to be transported through to change the DNA topology. Despite the central importance of this gate-opening event to Top2 function, the DNA-gate in all reported structures of Top2-DNA complexes is in the closed state. Here we present the crystal structure of a human Top2 DNA-gate in an open conformation, which not only reveals structural characteristics of its DNA-conducting path, but also uncovers unexpected yet functionally significant conformational changes associated with gate-opening. This structure further implicates Top2's preference for a left-handed DNA braid and allows the construction of a model representing the initial entry of another DNA duplex into the DNA-gate. Steered molecular dynamics calculations suggests the Top2-catalyzed DNA passage may be achieved by a rocker-switch-type movement of the DNA-gate.
Structural insights into the gating of DNA passage by the topoisomerase II DNA-gate.,Chen SF, Huang NL, Lin JH, Wu CC, Wang YR, Yu YJ, Gilson MK, Chan NL Nat Commun. 2018 Aug 6;9(1):3085. doi: 10.1038/s41467-018-05406-y. PMID:30082834[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ West KL, Meczes EL, Thorn R, Turnbull RM, Marshall R, Austin CA. Mutagenesis of E477 or K505 in the B' domain of human topoisomerase II beta increases the requirement for magnesium ions during strand passage. Biochemistry. 2000 Feb 15;39(6):1223-33. PMID:10684600
- ↑ Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S. The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome. Cell. 2003 Jun 27;113(7):905-17. PMID:12837248
- ↑ Chen SF, Huang NL, Lin JH, Wu CC, Wang YR, Yu YJ, Gilson MK, Chan NL. Structural insights into the gating of DNA passage by the topoisomerase II DNA-gate. Nat Commun. 2018 Aug 6;9(1):3085. doi: 10.1038/s41467-018-05406-y. PMID:30082834 doi:http://dx.doi.org/10.1038/s41467-018-05406-y
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