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==Crystal structure of an engineered helicase domain construct for human Bloom syndrome protein (BLM)==
==Crystal structure of an engineered helicase domain construct for human Bloom syndrome protein (BLM)==
<StructureSection load='7auc' size='340' side='right'caption='[[7auc]]' scene=''>
<StructureSection load='7auc' size='340' side='right'caption='[[7auc]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AUC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7AUC FirstGlance]. <br>
<table><tr><td colspan='2'>[[7auc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AUC FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7auc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7auc OCA], [http://pdbe.org/7auc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7auc RCSB], [http://www.ebi.ac.uk/pdbsum/7auc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7auc ProSAT]</span></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BLM, RECQ2, RECQL3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=7auc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7auc OCA], [https://pdbe.org/7auc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7auc RCSB], [https://www.ebi.ac.uk/pdbsum/7auc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7auc ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/BLM_HUMAN BLM_HUMAN]] Bloom syndrome. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[[https://www.uniprot.org/uniprot/BLM_HUMAN BLM_HUMAN]] Participates in DNA replication and repair. Exhibits a magnesium-dependent ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3'-5' direction. Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA. Negatively regulates sister chromatid exchange (SCE).<ref>PMID:9388193</ref> <ref>PMID:12019152</ref> <ref>PMID:21325134</ref> <ref>PMID:23509288</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BLM (Bloom syndrome protein) is a RECQ-family helicase involved in the dissolution of complex DNA structures and repair intermediates. Synthetic lethality analysis implicates BLM as a promising target in a range of cancers with defects in the DNA damage response; however, selective small molecule inhibitors of defined mechanism are currently lacking. Here, we identify and characterise a specific inhibitor of BLM's ATPase-coupled DNA helicase activity, by allosteric trapping of a DNA-bound translocation intermediate. Crystallographic structures of BLM-DNA-ADP-inhibitor complexes identify a hitherto unknown interdomain interface, whose opening and closing are integral to translocation of ssDNA, and which provides a highly selective pocket for drug discovery. Comparison with structures of other RECQ helicases provides a model for branch migration of Holliday junctions by BLM.
Uncovering an allosteric mode of action for a selective inhibitor of human Bloom syndrome protein.,Chen X, Ali YI, Fisher CE, Arribas-Bosacoma R, Rajasekaran MB, Williams G, Walker S, Booth JR, Hudson JJ, Roe SM, Pearl LH, Ward SE, Pearl FM, Oliver AW Elife. 2021 Mar 1;10. pii: 65339. doi: 10.7554/eLife.65339. PMID:33647232<ref>PMID:33647232</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7auc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Chen X]]
[[Category: Chen, X]]
[[Category: Oliver AW]]
[[Category: Oliver, A W]]
[[Category: Blm]]
[[Category: Dna repair]]
[[Category: Helicase]]
[[Category: Nuclear protein]]
[[Category: Recq]]
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