View source for 4cgy


==Crystal structure of the human topoisomerase III alpha-RMI1 complex==
<StructureSection load='4cgy' size='340' side='right'caption='[[4cgy]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4cgy]] is a 2 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=4CGY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CGY 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]] 2.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=4cgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cgy OCA], [https://pdbe.org/4cgy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cgy RCSB], [https://www.ebi.ac.uk/pdbsum/4cgy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cgy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TOP3A_HUMAN TOP3A_HUMAN] Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Has DNA decatenation activity.<ref>PMID:8622991</ref> <ref>PMID:20445207</ref> 
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== Publication Abstract from PubMed ==
Repair of DNA double-strand breaks via homologous recombination can produce double Holliday junctions (dHJs) that require enzymatic separation. Topoisomerase IIIalpha (TopIIIalpha) together with RMI1 disentangles the final hemicatenane intermediate obtained once dHJs have converged. How binding of RMI1 to TopIIIalpha influences it to behave as a hemicatenane dissolvase, rather than as an enzyme that relaxes DNA topology, is unknown. Here, we present the crystal structure of human TopIIIalpha complexed to the first oligonucleotide-binding domain (OB fold) of RMI1. TopIII assumes a toroidal type 1A topoisomerase fold. RMI1 attaches to the edge of the gate in TopIIIalpha through which DNA passes. RMI1 projects a 23-residue loop into the TopIIIalpha gate, thereby influencing the dynamics of its opening and closing. Our results provide a mechanistic rationale for how RMI1 stabilizes TopIIIalpha-gate opening to enable dissolution and illustrate how binding partners modulate topoisomerase function.

Structural and mechanistic insight into Holliday-junction dissolution by Topoisomerase IIIalpha and RMI1.,Bocquet N, Bizard AH, Abdulrahman W, Larsen NB, Faty M, Cavadini S, Bunker RD, Kowalczykowski SC, Cejka P, Hickson ID, Thoma NH Nat Struct Mol Biol. 2014 Feb 9. doi: 10.1038/nsmb.2775. PMID:24509834<ref>PMID:24509834</ref>

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

==See Also==
*[[Topoisomerase 3D structures|Topoisomerase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bocquet N]]
[[Category: Bunker RD]]
[[Category: Thoma NH]]