4g2f | pdb_00004g2f

Human EphA3 kinase domain in complex with compound 7

spinqualitylabelsall models 4g2f, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4g2f is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: C07 Gene: EPHA3 (HUMAN) Activity: Receptor protein-tyrosine kinase, with EC number 2.7.10.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed We have discovered a novel chemical class of inhibitors of the EphB4 tyrosine kinase by fragment-based high-throughput docking followed by explicit solvent molecular dynamics simulations for assessment of the binding mode. The synthesis of a single derivative (compound 7) of the hit identified in silico has resulted in an improvement of the inhibitory potency in an enzymatic assay from 8.4 muM to 160 nM and a ligand efficiency of 0.39 kcal/mol per non-hydrogen atom. Such remarkable improvement in affinity is due to an additional hydroxyl group involved in two favorable (buried) hydrogen bonds as predicted by molecular dynamics and validated by the crystal structure of the complex with EphA3 solved at 1.7 A resolution. Discovery of a novel chemotype of tyrosine kinase inhibitors by fragment-based docking and molecular dynamics.,Zhao H, Dong J, Lafleur K, Nevado C, Caflisch A ACS Med Chem Lett. 2012 Aug 23;3(10):834-8. doi: 10.1021/ml3001984. eCollection, 2012 Oct 11. PMID:24900387 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ephrin receptor

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