4g0u: Difference between revisions

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{{STRUCTURE_4g0u| PDB=4g0u | SCENE= }}
==Human topoisomerase IIbeta in complex with DNA and amsacrine==
===Human topoisomerase IIbeta in complex with DNA and amsacrine===
<StructureSection load='4g0u' size='340' side='right' caption='[[4g0u]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
{{ABSTRACT_PUBMED_24038465}}
== Structural highlights ==
<table><tr><td colspan='2'>[[4g0u]] is a 6 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=4G0U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G0U FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ASW:N-[4-(ACRIDIN-9-YLAMINO)-3-METHOXYPHENYL]METHANESULFONAMIDE'>ASW</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">[[3qx3|3qx3]], [[4g0v|4g0v]], [[4g0w|4g0w]], [[4j3n|4j3n]]</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='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=4g0u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g0u OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4g0u RCSB], [http://www.ebi.ac.uk/pdbsum/4g0u PDBsum]</span></td></tr>
</table>
== 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Type II topoisomerases (Top2s) alter DNA topology via the formation of an enzyme-DNA adduct termed cleavage complex, which harbors a transient double-strand break in one DNA to allow the passage of another. Agents targeting human Top2s are clinically active anticancer drugs whose trapping of Top2-mediated DNA breakage effectively induces genome fragmentation and cell death. To understand the structural basis of this drug action, we previously determined the structure of human Top2 beta-isoform forming a cleavage complex with the drug etoposide and DNA, and described the insertion of drug into DNA cleavage site and drug-induced decoupling of catalytic groups. By developing a post-crystallization drug replacement procedure that simplifies structural characterization of drug-stabilized cleavage complexes, we have extended the analysis toward other structurally distinct drugs, m-AMSA and mitoxantrone. Besides the expected drug intercalation, a switch in ribose puckering in the 3'-nucleotide of the cleavage site was robustly observed in the new structures, representing a new mechanism for trapping the Top2 cleavage complex. Analysis of drug-binding modes and the conformational landscapes of the drug-binding pockets provide rationalization of the drugs' structural-activity relationships and explain why Top2 mutants exhibit differential effects toward each drug. Drug design guidelines were proposed to facilitate the development of isoform-specific Top2-targeting anticancer agents.


==Function==
On the structural basis and design guidelines for type II topoisomerase-targeting anticancer drugs.,Wu CC, Li YC, Wang YR, Li TK, Chan NL Nucleic Acids Res. 2013 Sep 14. PMID:24038465<ref>PMID:24038465</ref>
[[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>


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[4g0u]] is a 6 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=4G0U OCA].
</div>


==See Also==
==See Also==
*[[Topoisomerase|Topoisomerase]]
*[[Topoisomerase|Topoisomerase]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:024038465</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Human]]
[[Category: Chan, N L.]]
[[Category: Chan, N L]]
[[Category: Li, T K.]]
[[Category: Li, T K]]
[[Category: Li, Y C.]]
[[Category: Li, Y C]]
[[Category: Wu, C C.]]
[[Category: Wu, C C]]
[[Category: Coiled-coil domain]]
[[Category: Coiled-coil domain]]
[[Category: Dna-binding and cleavage]]
[[Category: Dna-binding and cleavage]]
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