2OIQ
Crystal Structure of chicken c-Src kinase domain in complex with the cancer drug imatinib.
Summary for 2OIQ
| Entry DOI | 10.2210/pdb2oiq/pdb |
| Descriptor | Proto-oncogene tyrosine-protein kinase Src, 4-(4-METHYL-PIPERAZIN-1-YLMETHYL)-N-[4-METHYL-3-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-PHENYL]-BENZAMIDE, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | src, kinase, imatinib, inactive, transferase |
| Biological source | Gallus gallus (chicken) |
| Total number of polymer chains | 2 |
| Total formula weight | 66131.08 |
| Authors | Seeliger, M.A.,Nagar, B.,Frank, F.,Cao, X.,Henderson, M.N.,Kuriyan, J. (deposition date: 2007-01-11, release date: 2007-03-20, Last modification date: 2023-08-30) |
| Primary citation | Seeliger, M.A.,Nagar, B.,Frank, F.,Cao, X.,Henderson, M.N.,Kuriyan, J. c-Src Binds to the Cancer Drug Imatinib with an Inactive Abl/c-Kit Conformation and a Distributed Thermodynamic Penalty. Structure, 15:299-311, 2007 Cited by PubMed Abstract: The cancer drug imatinib inhibits the tyrosine kinases c-Abl, c-Kit, and the PDGF receptor. Imatinib is less effective against c-Src, which is difficult to understand because residues interacting with imatinib in crystal structures of Abl and c-Kit are conserved in c-Src. The crystal structure of the c-Src kinase domain in complex with imatinib closely resembles that of Abl*imatinib and c-Kit*imatinib, and differs significantly from the inactive "Src/CDK" conformation of the Src family kinases. Attempts to increase the affinity of c-Src for imatinib by swapping residues with the corresponding residues in Abl have not been successful, suggesting that the thermodynamic penalty for adoption of the imatinib-binding conformation by c-Src is distributed over a broad region of the structure. Two mutations that are expected to destabilize the inactive Src/CDK conformation increase drug sensitivity 15-fold, suggesting that the free-energy balance between different inactive states is a key to imatinib binding. PubMed: 17355866DOI: 10.1016/j.str.2007.01.015 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.07 Å) |
Structure validation
Download full validation report
