4DGG
c-SRC kinase domain in complex with RM-1-176
Summary for 4DGG
| Entry DOI | 10.2210/pdb4dgg/pdb |
| Related | 3uqf 3uqg |
| Descriptor | Proto-oncogene tyrosine-protein kinase Src, 3-{6-[(3-chlorobenzyl)oxy]naphthalen-2-yl}-1-(propan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (3 entities in total) |
| Functional Keywords | tyrosine protein kinase, atp-binding, kinase domain, transferase |
| Biological source | Gallus gallus (bantam,chickens) |
| Cellular location | Cell membrane (By similarity): P00523 |
| Total number of polymer chains | 2 |
| Total formula weight | 66341.15 |
| Authors | Merritt, E.A.,Larson, E.T. (deposition date: 2012-01-25, release date: 2012-10-10, Last modification date: 2024-02-28) |
| Primary citation | Krishnamurty, R.,Brigham, J.L.,Leonard, S.E.,Ranjitkar, P.,Larson, E.T.,Dale, E.J.,Merritt, E.A.,Maly, D.J. Active site profiling reveals coupling between domains in SRC-family kinases. Nat.Chem.Biol., 9:43-50, 2013 Cited by PubMed Abstract: Protein kinases, key regulators of intracellular signal transduction, have emerged as an important class of drug targets. Chemical proteomic tools that facilitate the functional interrogation of protein kinase active sites are powerful reagents for studying the regulation of this large enzyme family and performing inhibitor selectivity screens. Here we describe a new crosslinking strategy that enables rapid and quantitative profiling of protein kinase active sites in lysates and live cells. Applying this methodology to the SRC-family kinases (SFKs) SRC and HCK led to the identification of a series of conformation-specific, ATP-competitive inhibitors that have a distinct preference for the autoinhibited forms of these kinases. Furthermore, we show that ligands that have this selectivity are able to modulate the ability of the regulatory domains of SRC and HCK to engage in intermolecular binding interactions. These studies provide insight into the regulation of this important family of tyrosine kinases. PubMed: 23143416DOI: 10.1038/nchembio.1118 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.65 Å) |
Structure validation
Download full validation report
