7AUC
Crystal structure of an engineered helicase domain construct for human Bloom syndrome protein (BLM)
Summary for 7AUC
| Entry DOI | 10.2210/pdb7auc/pdb |
| Descriptor | Bloom syndrome protein,Bloom syndrome protein, ACETATE ION, 1,2-ETHANEDIOL, ... (10 entities in total) |
| Functional Keywords | helicase, recq, blm, dna repair, nuclear protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 65594.97 |
| Authors | Chen, X.,Oliver, A.W. (deposition date: 2020-11-02, release date: 2020-12-16, Last modification date: 2024-01-31) |
| Primary citation | Chen, X.,Ali, Y.I.,Fisher, C.E.,Arribas-Bosacoma, R.,Rajasekaran, M.B.,Williams, G.,Walker, S.,Booth, J.R.,Hudson, J.J.,Roe, S.M.,Pearl, L.H.,Ward, S.E.,Pearl, F.M.,Oliver, A.W. Uncovering an allosteric mode of action for a selective inhibitor of human Bloom syndrome protein. Elife, 10:-, 2021 Cited by PubMed Abstract: 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. PubMed: 33647232DOI: 10.7554/eLife.65339 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.53 Å) |
Structure validation
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