3uol | pdb_00003uol

Aurora A in complex with SO2-162

spinqualitylabelsall models 3uol, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3uol is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 0C7, EDO Related: 3unj, 3unk, 3unz, 3uo4, 3uo5, 3uo6, 3uod, 3uoh, 3uoj, 3uok, 3up2, 3up7 Gene: AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 (Homo sapiens) Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Most protein kinases share a DFG (Asp-Phe-Gly) motif in the ATP site which can assume two distinct conformations, the active DFG-in and the inactive DFG-out states. Small molecule inhibitors able to induce the DFG-out state have received considerable attention in kinase drug discovery. Using a typical DFG-in inhibitor scaffold of Aurora A, a kinase involved in the regulation of cell division, we found that halogen and nitrile substituents directed at the N-terminally flanking residue Ala273 induced global conformational changes in the enzyme, leading to DFG-out inhibitors that are among the most potent Aurora A inhibitors reported to date. The data suggest an unprecedented mechanism of action, in which induced-dipole forces along the Ala273 side chain alter the charge distribution of the DFG backbone, allowing the DFG to unwind. As the ADFG sequence and three-dimensional structure is highly conserved, DFG-out inhibitors of other kinases may be designed by specifically targeting the flanking alanine residue with electric dipoles. A novel mechanism by which small molecule inhibitors induce the DFG flip in Aurora A.,Martin MP, Zhu JY, Lawrence H, Pireddu R, Luo Y, Alam R, Ozcan S, Sebti SM, Lawrence NJ, Schonbrunn E ACS Chem Biol. 2012 Jan 16. PMID:22248356 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine/threonine protein kinase

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