9RUR
Structure of WRN in complex with ATPgS and covalent ligand Compound 4d
This is a non-PDB format compatible entry.
Summary for 9RUR
| Entry DOI | 10.2210/pdb9rur/pdb |
| Related | 9RTI |
| Descriptor | Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER, DIMETHYL SULFOXIDE, ... (9 entities in total) |
| Functional Keywords | dna damage repair, inhibitor, complex, helicase, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 100053.55 |
| Authors | Fletcher, C.T.,Rucktooa, P. (deposition date: 2025-07-04, release date: 2025-10-22, Last modification date: 2025-11-05) |
| Primary citation | Smith, G.M.T.,Aithani, L.,Barrett, C.E.,Bucher, A.O.,Cooper, C.D.O.,Degorce, S.L.,Dore, A.S.,Fletcher, C.T.,Huber, S.,Huckvale, R.,Kennedy, A.J.,Mornement, A.A.,Pickworth, M.,Rucktooa, P.,Scully, C.C.G.,Skerratt, S.E. AI-assisted delivery of novel covalent WRN inhibitors from a non-covalent fragment screen. Bioorg.Med.Chem.Lett., 131:130421-130421, 2025 Cited by PubMed Abstract: Werner (WRN) helicase, has emerged as a promising therapeutic target for cancers associated with microsatellite instability (MSI). This letter describes the discovery of small molecule inhibitors from a fragment screen that occupy a cryptic, allosteric site of WRN helicase. Key findings include the identification of benzimidazole and amino-indazole scaffolds, exploiting their proximity to Cys727 via covalent modification. The use of our proprietary co-folding model DragonFold assisted the identification of novel WRN helicase inhibitors. These, together with near-neighbor profiling, offer tools for furthering the understanding of WRN and BLM helicase function, and potential therapeutic avenues for MSI-associated cancers. PubMed: 41038585DOI: 10.1016/j.bmcl.2025.130421 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.296 Å) |
Structure validation
Download full validation report
