8Q6H
HUMAN PI4KIIIB IN COMPLEX WITH COVALENTLY BOUND INHIBITOR (COMPOUND 11)
Summary for 8Q6H
| Entry DOI | 10.2210/pdb8q6h/pdb |
| Descriptor | Phosphatidylinositol 4-kinase beta, MAGNESIUM ION, 3-(3-fluorosulfonyloxy-4-methoxy-phenyl)-7-[(4-fluorosulfonyloxyphenyl)methylamino]-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine, ... (5 entities in total) |
| Functional Keywords | lipid kinase, transferase-signaling protein complex, covalent inhibitor., transferase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 49044.54 |
| Authors | Somers, D.O. (deposition date: 2023-08-11, release date: 2023-12-13, Last modification date: 2024-11-13) |
| Primary citation | Cosgrove, B.,Grant, E.K.,Bertrand, S.,Down, K.D.,Somers, D.O.,P Evans, J.,Tomkinson, N.C.O.,Barker, M.D. Covalent targeting of non-cysteine residues in PI4KIII beta. Rsc Chem Biol, 4:1111-1122, 2023 Cited by PubMed Abstract: The synthesis and characterisation of fluorosulfate covalent inhibitors of the lipid kinase PI4KIIIβ is described. The conserved lysine residue located within the ATP binding site was targeted, and optimised compounds based upon reversible inhibitors with good activity and physicochemical profile showed strong reversible interactions and slow onset times for the covalent inhibition, resulting in an excellent selectivity profile for the lipid kinase target. X-Ray crystallography demonstrated a distal tyrosine residue could also be targeted using a fluorosulfate strategy. Combination of this knowledge showed that a dual covalent inhibitor could be developed which reveals potential in addressing the challenges associated with drug resistant mutations. PubMed: 38033723DOI: 10.1039/d3cb00142c PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.94 Å) |
Structure validation
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