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{{STRUCTURE_4g0u|  PDB=4g0u  |  SCENE=  }}
===Human topoisomerase IIbeta in complex with DNA and amsacrine===
{{ABSTRACT_PUBMED_24038465}}


==Function==
==Human topoisomerase IIbeta in complex with DNA and amsacrine==
[[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>
<StructureSection load='4g0u' size='340' side='right'caption='[[4g0u]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4g0u]] 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=4G0U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G0U FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4g0u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g0u OCA], [https://pdbe.org/4g0u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g0u RCSB], [https://www.ebi.ac.uk/pdbsum/4g0u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g0u ProSAT]</span></td></tr>
</table>
== 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;">
== 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.


==About this Structure==
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>
[[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].
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4g0u" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Topoisomerase|Topoisomerase]]
*[[Topoisomerase 3D structures|Topoisomerase 3D structures]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:024038465</ref><references group="xtra"/><references/>
__TOC__
[[Category: Human]]
</StructureSection>
[[Category: Chan, N L.]]
[[Category: Homo sapiens]]
[[Category: Li, T K.]]
[[Category: Large Structures]]
[[Category: Li, Y C.]]
[[Category: Chan NL]]
[[Category: Wu, C C.]]
[[Category: Li TK]]
[[Category: Coiled-coil domain]]
[[Category: Li YC]]
[[Category: Dna-binding and cleavage]]
[[Category: Wu CC]]
[[Category: Isomerase-dna-isomerase inhibitor complex]]
[[Category: Nucleus]]
[[Category: Toprim domain]]
[[Category: Winged-helix domain]]
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