6lk0

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<StructureSection load='6lk0' size='340' side='right'caption='[[6lk0]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='6lk0' size='340' side='right'caption='[[6lk0]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6lk0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LK0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6LK0 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6lk0]] is a 1 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=6LK0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6LK0 FirstGlance]. <br>
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</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=6lk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lk0 OCA], [http://pdbe.org/6lk0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lk0 RCSB], [http://www.ebi.ac.uk/pdbsum/6lk0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lk0 ProSAT]</span></td></tr>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRIP13, PCH2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<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=6lk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lk0 OCA], [http://pdbe.org/6lk0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lk0 RCSB], [http://www.ebi.ac.uk/pdbsum/6lk0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lk0 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/PCH2_HUMAN PCH2_HUMAN]] Plays a key role in chromosome recombination and chromosome structure development during meiosis. Required at early steps in meiotic recombination that leads to non-crossovers pathways. Also needed for efficient completion of homologous synapsis by influencing crossover distribution along the chromosomes affecting both crossovers and non-crossovers pathways. Also required for development of higher-order chromosome structures and is needed for synaptonemal-complex formation. In males, required for efficient synapsis of the sex chromosomes and for sex body formation. Promotes early steps of the DNA double-strand breaks (DSBs) repair process upstream of the assembly of RAD51 complexes. Required for depletion of HORMAD1 and HORMAD2 from synapsed chromosomes (By similarity).
[[http://www.uniprot.org/uniprot/PCH2_HUMAN PCH2_HUMAN]] Plays a key role in chromosome recombination and chromosome structure development during meiosis. Required at early steps in meiotic recombination that leads to non-crossovers pathways. Also needed for efficient completion of homologous synapsis by influencing crossover distribution along the chromosomes affecting both crossovers and non-crossovers pathways. Also required for development of higher-order chromosome structures and is needed for synaptonemal-complex formation. In males, required for efficient synapsis of the sex chromosomes and for sex body formation. Promotes early steps of the DNA double-strand breaks (DSBs) repair process upstream of the assembly of RAD51 complexes. Required for depletion of HORMAD1 and HORMAD2 from synapsed chromosomes (By similarity).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The AAA-ATPase TRIP13 drives multiple myeloma (MM) progression. Here we present the crystal structure of wild-type human TRIP13 at a resolution of 2.6 A. A small molecule inhibitor targeting TRIP13 was identified based on the crystal structure. The inhibitor, designated DCZ0415, was confirmed to bind TRIP13 using pull-down, nuclear magnetic resonance spectroscopy, and surface plasmon resonance binding assays. DCZ0415 induced anti-myeloma activity in vitro, in vivo, and in primary cells derived from drug-resistant myeloma patients. The inhibitor impaired nonhomologous end joining repair and inhibited NF-kappaB activity. Moreover, combining DCZ0415 with the MM chemotherapeutic melphalan or the HDAC inhibitor panobinostat induced synergistic anti-myeloma activity. Therefore, targeting TRIP13 may be an effective therapeutic strategy for MM, particularly refractory or relapsed MM.
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A Small Molecule Inhibitor Targeting TRIP13 suppresses multiple myeloma progression.,Wang Y, Huang J, Li B, Xue H, Tricot G, Hu L, Xu Z, Sun X, Chang S, Gao L, Tao Y, Xu H, Xie Y, Xiao W, Yu D, Kong Y, Chen G, Sun X, Lian F, Zhang N, Wu X, Mao Z, Zhan F, Zhu W, Shi J Cancer Res. 2019 Nov 15. pii: 0008-5472.CAN-18-3987. doi:, 10.1158/0008-5472.CAN-18-3987. PMID:31732653<ref>PMID:31732653</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6lk0" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Chang, S]]
[[Category: Chang, S]]

Revision as of 16:12, 29 January 2020

Crystal structure of human wild type TRIP13

PDB ID 6lk0

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