7zbg

From Proteopedia

(Difference between revisions)

Current revision

Human Topoisomerase II Beta ATPase ADP

Structural highlights

7zbg is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Human topoisomerase II beta (TOP2B) modulates DNA topology using energy from ATP hydrolysis. To investigate the conformational changes that occur during ATP hydrolysis, we determined the X-ray crystallographic structures of the human TOP2B ATPase domain bound to AMPPNP or ADP at 1.9 A and 2.6 A resolution, respectively. The GHKL domains of both structures are similar, whereas the QTK loop within the transducer domain can move for product release. As TOP2B is the clinical target of bisdioxopiperazines, we also determined the structure of a TOP2B:ADP:ICRF193 complex to 2.3 A resolution and identified key drug-binding residues. Biochemical characterization revealed the N-terminal strap reduces the rate of ATP hydrolysis. Mutagenesis demonstrated residue E103 as essential for ATP hydrolysis in TOP2B. Our data provide fundamental insights into the tertiary structure of the human TOP2B ATPase domain and a potential regulatory mechanism for ATP hydrolysis.

A comprehensive structural analysis of the ATPase domain of human DNA topoisomerase II beta bound to AMPPNP, ADP, and the bisdioxopiperazine, ICRF193.,Ling EM, Basle A, Cowell IG, van den Berg B, Blower TR, Austin CA Structure. 2022 Aug 4;30(8):1129-1145.e3. doi: 10.1016/j.str.2022.05.009. Epub , 2022 Jun 3. PMID:35660158^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Ling EM, Basle A, Cowell IG, van den Berg B, Blower TR, Austin CA. A comprehensive structural analysis of the ATPase domain of human DNA topoisomerase II beta bound to AMPPNP, ADP, and the bisdioxopiperazine, ICRF193. Structure. 2022 Aug 4;30(8):1129-1145.e3. doi: 10.1016/j.str.2022.05.009. Epub , 2022 Jun 3. PMID:35660158 doi:http://dx.doi.org/10.1016/j.str.2022.05.009

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7zbg"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[7zbg]] is a 1 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=7ZBG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZBG FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ITH:4-[(2S,3R)-3-[3,5-bis(oxidanylidene)piperazin-1-ium-1-yl]butan-2-yl]piperazin-4-ium-2,6-dione'>ITH</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ITH:4-[(2S,3R)-3-[3,5-bis(oxidanylidene)piperazin-1-ium-1-yl]butan-2-yl]piperazin-4-ium-2,6-dione'>ITH</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7zbg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zbg OCA], [https://pdbe.org/7zbg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zbg RCSB], [https://www.ebi.ac.uk/pdbsum/7zbg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zbg ProSAT]</span></td></tr>
 </table>
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 7zbg" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Topoisomerase 3D structures|Topoisomerase 3D structures]]
 == References ==
 <references/>

7zbg

From Proteopedia

Current revision

Human Topoisomerase II Beta ATPase ADP

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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