4LGH
Crystal structure of 1NM-PP1 bound to analog-sensitive Src kinase
Summary for 4LGH
| Entry DOI | 10.2210/pdb4lgh/pdb |
| Related | 4LGG |
| Descriptor | Proto-oncogene tyrosine-protein kinase Src, 1-tert-butyl-3-(naphthalen-1-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (3 entities in total) |
| Functional Keywords | kinase domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Gallus gallus (bantam,chickens) |
| Cellular location | Cell membrane : P00523 |
| Total number of polymer chains | 2 |
| Total formula weight | 64177.93 |
| Authors | Lopez, M.S.,Dar, A.C.,Shokat, K.M. (deposition date: 2013-06-27, release date: 2013-08-07, Last modification date: 2023-09-20) |
| Primary citation | Zhang, C.,Lopez, M.S.,Dar, A.C.,Ladow, E.,Finkbeiner, S.,Yun, C.H.,Eck, M.J.,Shokat, K.M. Structure-guided inhibitor design expands the scope of analog-sensitive kinase technology. Acs Chem.Biol., 8:1931-1938, 2013 Cited by PubMed Abstract: Engineered analog-sensitive (AS) protein kinases have emerged as powerful tools for dissecting phospho-signaling pathways, for elucidating the cellular function of individual kinases, and for deciphering unanticipated effects of clinical therapeutics. A crucial and necessary feature of this technology is a bioorthogonal small molecule that is innocuous toward native cellular systems but potently inhibits the engineered kinase. In order to generalize this method, we sought a molecule capable of targeting divergent AS-kinases. Here we employ X-ray crystallography and medicinal chemistry to unravel the mechanism of current inhibitors and use these insights to design the most potent, selective, and general AS-kinase inhibitors reported to date. We use large-scale kinase inhibitor profiling to characterize the selectivity of these molecules as well as examine the consequences of potential off-target effects in chemical genetic experiments. The molecules reported here will serve as powerful tools in efforts to extend AS-kinase technology to the entire kinome and the principles discovered may help in the design of other engineered enzyme/ligand pairs. PubMed: 23841803DOI: 10.1021/cb400376p PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.84 Å) |
Structure validation
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