View source for 7aud


==Structure of an engineered helicase domain construct for human Bloom syndrome protein (BLM)==
<StructureSection load='7aud' size='340' side='right'caption='[[7aud]], [[Resolution|resolution]] 2.96&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7aud]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AUD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AUD 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]] 2.96&#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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=RY8:N-(2,3-dimethyl-5-sulfamoylphenyl)-4-(2-methylthiazol-4-yl)benzamide'>RY8</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7aud FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aud OCA], [https://pdbe.org/7aud PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aud RCSB], [https://www.ebi.ac.uk/pdbsum/7aud PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aud ProSAT]</span></td></tr>
</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 7aud" style="background-color:#fffaf0;"></div>

==See Also==
*[[Helicase 3D structures|Helicase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Chen X]]
[[Category: Oliver AW]]