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[[ | ==Human topoisomerase IIbeta in complex with DNA and etoposide== | ||
<StructureSection load='3qx3' size='340' side='right' caption='[[3qx3]], [[Resolution|resolution]] 2.16Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3qx3]] is a 6 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=3QX3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QX3 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qxk|3qxk]]</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 Homo sapiens])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3qx3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qx3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qx3 RCSB], [http://www.ebi.ac.uk/pdbsum/3qx3 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Type 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<ref>PMID:21778401</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Topoisomerase|Topoisomerase]] | *[[Topoisomerase|Topoisomerase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Chan, N L | [[Category: Chan, N L]] | ||
[[Category: Chiang, C W | [[Category: Chiang, C W]] | ||
[[Category: Farh, L | [[Category: Farh, L]] | ||
[[Category: Li, T K | [[Category: Li, T K]] | ||
[[Category: Lin, L Y | [[Category: Lin, L Y]] | ||
[[Category: Lin, T S | [[Category: Lin, T S]] | ||
[[Category: Wu, C C | [[Category: Wu, C C]] | ||
[[Category: Yen, T J | [[Category: Yen, T J]] | ||
[[Category: Yu, Y J | [[Category: Yu, Y J]] | ||
[[Category: Coiled-coil domain]] | [[Category: Coiled-coil domain]] | ||
[[Category: Dna binding and cleavage]] | [[Category: Dna binding and cleavage]] | ||
Revision as of 14:49, 9 December 2014
Human topoisomerase IIbeta in complex with DNA and etoposideHuman topoisomerase IIbeta in complex with DNA and etoposide
Structural highlights
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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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