3LOK
Drug resistant cSrc kinase domain in complex with covalent inhibitor PD168393
Summary for 3LOK
| Entry DOI | 10.2210/pdb3lok/pdb |
| Related | 2HWP 2QI8 2QLQ 2QQ7 |
| Descriptor | Proto-oncogene tyrosine-protein kinase Src, N-[4-(3-BROMO-PHENYLAMINO)-QUINAZOLIN-6-YL]-ACRYLAMIDE (3 entities in total) |
| Functional Keywords | src kinase domain, drug resistance, irreversible inhibitor, covalent inhibitor, pd168393, atp-binding, kinase, lipoprotein, myristate, nucleotide-binding, phosphoprotein, proto-oncogene, sh2 domain, sh3 domain, tyrosine-protein kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Gallus gallus (chicken) |
| Cellular location | Cell membrane (By similarity): P00523 |
| Total number of polymer chains | 2 |
| Total formula weight | 66284.03 |
| Authors | Gruetter, C.,Rode, H.B.,Rauh, D. (deposition date: 2010-02-04, release date: 2010-12-22, Last modification date: 2024-11-13) |
| Primary citation | Klueter, S.,Simard, J.R.,Rode, H.B.,Gruetter, C.,Pawar, V.,Raaijmakers, H.C.,Barf, T.A.,Rabiller, M.,van Otterlo, W.A.L.,Rauh, D. Characterization of irreversible kinase inhibitors by directly detecting covalent bond formation: a tool for dissecting kinase drug resistance Chembiochem, 11:2557-2566, 2010 Cited by PubMed Abstract: Targeting protein kinases in cancer therapy with irreversible small-molecule inhibitors is moving to the forefront of kinase-inhibitor research and is thought to be an effective means of overcoming mutation-associated drug resistance in epidermal growth factor receptor kinase (EGFR). We generated a detection technique that allows direct measurements of covalent bond formation without relying on kinase activity, thereby allowing the straightforward investigation of the influence of steric clashes on covalent inhibitors in different resistant kinase mutants. The obtained results are discussed together with structural biology and biochemical studies of catalytic activity in both wild-type and gatekeeper mutated kinase variants to draw conclusions about the impact of steric hindrance and increased catalytic activity in drug-resistant kinase variants. PubMed: 21080395DOI: 10.1002/cbic.201000352 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.48 Å) |
Structure validation
Download full validation report
