9ZLJ
Crystal structure of BTK kinase domain bound to compound YS1
This is a non-PDB format compatible entry.
Summary for 9ZLJ
| Entry DOI | 10.2210/pdb9zlj/pdb |
| Descriptor | Tyrosine-protein kinase BTK, N-{(1r,4r)-4-[2-(4-chlorophenoxy)acetamido]cyclohexyl}-N-[2-(4-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)ethyl]propanamide, IMIDAZOLE, ... (4 entities in total) |
| Functional Keywords | inhibitor, kinase, transferase-transferase inhibitor complex, transferase, transferase/transferase inhibitor |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 32811.08 |
| Authors | Lin, D.Y.,Shamir, Y.,Gaibzon, R.,Rogel, A.,Andreotti, A.H.,London, N. (deposition date: 2025-12-08, release date: 2026-02-25, Last modification date: 2026-04-08) |
| Primary citation | Shamir, Y.,Gabizon, R.,Rogel, A.,Lin, D.Y.,Andreotti, A.H.,London, N. Discovery of Covalent Ligands with AlphaFold3. J.Am.Chem.Soc., 148:13043-13054, 2026 Cited by PubMed Abstract: Covalent inhibitors are a prominent modality for research and therapeutic tools. However, a scarcity of computational methods for their discovery slows progress in this field. AI models such as AlphaFold3 (AF3) have shown accuracy in ligand pose prediction, but their applicability for virtual screening campaigns was not assessed. We show that AF3 cofolding predictions and an associated predicted confidence metric ranks true covalent binders with near-optimal classification over property-matched decoys, significantly outperforming state-of-the-art covalent docking tools for a set of protein kinases. In a prospective virtual screening campaign against the model kinase BTK, we discovered a chemically distinct, novel, covalent small molecule that displays potent inhibition and in cells while maintaining marked kinome and proteomic selectivity. Co-crystallography validated the subangstrom accuracy of the predicted AF3 binding mode. These results demonstrate that AF3 can be practically used to discover novel chemical matter for kinases, one of the most prolific families of drug targets. PubMed: 41857796DOI: 10.1021/jacs.5c22222 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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