3qx3: Difference between revisions
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<StructureSection load='3qx3' size='340' side='right'caption='[[3qx3]], [[Resolution|resolution]] 2.16Å' scene=''> | <StructureSection load='3qx3' size='340' side='right'caption='[[3qx3]], [[Resolution|resolution]] 2.16Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3qx3]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3qx3]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QX3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QX3 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EVP:(5S,5AR,8AR,9R)-9-(4-HYDROXY-3,5-DIMETHOXYPHENYL)-8-OXO-5,5A,6,8,8A,9-HEXAHYDROFURO[3,4 6,7]NAPHTHO[2,3-D][1,3]DIOXOL-5-YL+4,6-O-[(1R)-ETHYLIDENE]-BETA-D-GLUCOPYRANOSIDE'>EVP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.162Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EVP:(5S,5AR,8AR,9R)-9-(4-HYDROXY-3,5-DIMETHOXYPHENYL)-8-OXO-5,5A,6,8,8A,9-HEXAHYDROFURO[3,4 6,7]NAPHTHO[2,3-D][1,3]DIOXOL-5-YL+4,6-O-[(1R)-ETHYLIDENE]-BETA-D-GLUCOPYRANOSIDE'>EVP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=3qx3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qx3 OCA], [https://pdbe.org/3qx3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qx3 RCSB], [https://www.ebi.ac.uk/pdbsum/3qx3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qx3 ProSAT]</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=3qx3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qx3 OCA], [https://pdbe.org/3qx3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qx3 RCSB], [https://www.ebi.ac.uk/pdbsum/3qx3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qx3 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[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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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chan | [[Category: Chan NL]] | ||
[[Category: Chiang | [[Category: Chiang CW]] | ||
[[Category: Farh | [[Category: Farh L]] | ||
[[Category: Li | [[Category: Li TK]] | ||
[[Category: Lin | [[Category: Lin LY]] | ||
[[Category: Lin | [[Category: Lin TS]] | ||
[[Category: Wu | [[Category: Wu CC]] | ||
[[Category: Yen | [[Category: Yen TJ]] | ||
[[Category: Yu | [[Category: Yu YJ]] | ||
Latest revision as of 20:15, 1 November 2023
Human topoisomerase IIbeta in complex with DNA and etoposideHuman topoisomerase IIbeta in complex with DNA and etoposide
Structural highlights
FunctionTOP2B_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 PubMedType II topoisomerases (TOP2s) resolve the topological problems of DNA by transiently cleaving both strands of a DNA duplex to form a cleavage complex through which another DNA segment can be transported. Several widely prescribed anticancer drugs increase the population of TOP2 cleavage complex, which leads to TOP2-mediated chromosome DNA breakage and death of cancer cells. We present the crystal structure of a large fragment of human TOP2beta complexed to DNA and to the anticancer drug etoposide to reveal structural details of drug-induced stabilization of a cleavage complex. The interplay between the protein, the DNA, and the drug explains the structure-activity relations of etoposide derivatives and the molecular basis of drug-resistant mutations. The analysis of protein-drug interactions provides information applicable for developing an isoform-specific TOP2-targeting strategy. Structural basis of type II topoisomerase inhibition by the anticancer drug etoposide.,Wu CC, Li TK, Farh L, Lin LY, Lin TS, Yu YJ, Yen TJ, Chiang CW, Chan NL Science. 2011 Jul 22;333(6041):459-62. PMID:21778401[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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