6AMV
Abl 1b Regulatory Module 'inhibiting state'
Summary for 6AMV
| Entry DOI | 10.2210/pdb6amv/pdb |
| Related | 6AMW |
| NMR Information | BMRB: 30331 |
| Descriptor | Tyrosine-protein kinase ABL1 (1 entity in total) |
| Functional Keywords | signaling protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 28350.39 |
| Authors | Kalodimos, C.G.,Saleh, T.,Rossi, P. (deposition date: 2017-08-11, release date: 2017-09-27, Last modification date: 2024-05-15) |
| Primary citation | Saleh, T.,Rossi, P.,Kalodimos, C.G. Atomic view of the energy landscape in the allosteric regulation of Abl kinase. Nat. Struct. Mol. Biol., 24:893-901, 2017 Cited by PubMed Abstract: The activity of protein kinases is often regulated in an intramolecular fashion by signaling domains, which feature several phosphorylation or protein-docking sites. How kinases integrate such distinct binding and signaling events to regulate their activities is unclear, especially in quantitative terms. We used NMR spectroscopy to show how structural elements within the Abl regulatory module (RM) synergistically generate a multilayered allosteric mechanism that enables Abl kinase to function as a finely tuned switch. We dissected the structure and energetics of the regulatory mechanism to precisely measure the effects of various activating or inhibiting stimuli on Abl kinase activity. The data provide a mechanistic basis explaining genetic observations and reveal a previously unknown activator region within Abl. Our findings show that drug-resistance mutations in the Abl RM exert their allosteric effect by promoting the activated state of Abl and not by decreasing the drug affinity for the kinase. PubMed: 28945248DOI: 10.1038/nsmb.3470 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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