4alh | pdb_00004alh

N-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH 3,5 dimethyl-4-phenyl-1,2- oxazole

spinqualitylabelsall models 4alh, resolution 1.97Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4alh is a 3 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 4a9p. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: A9P, EDO, SO4 Related: 1x0j, 2ydw, 2yek, 4a9e, 4a9f, 4a9h, 4a9i, 4a9j, 4a9m, 4a9n, 4a9o, 4akn Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Bromodomains are epigenetic reader modules that regulate gene transcription through their recognition of acetyl-lysine modified histone tails. Inhibitors of this protein-protein interaction have the potential to modulate multiple diseases as demonstrated by the profound anti-inflammatory and antiproliferative effects of a recently disclosed class of BET compounds. While these compounds were discovered using phenotypic assays, here we present a highly efficient alternative approach to find new chemical templates, exploiting the abundant structural knowledge that exists for this target class. A phenyl dimethyl isoxazole chemotype resulting from a focused fragment screen has been rapidly optimized through structure-based design, leading to a sulfonamide series showing anti-inflammatory activity in cellular assays. This proof-of-principle experiment demonstrates the tractability of the BET family and bromodomain target class to fragment-based hit discovery and structure-based lead optimization. Fragment-based discovery of bromodomain inhibitors part 2: optimization of phenylisoxazole sulfonamides.,Bamborough P, Diallo H, Goodacre JD, Gordon L, Lewis A, Seal JT, Wilson DM, Woodrow MD, Chung CW J Med Chem. 2012 Jan 26;55(2):587-96. Epub 2012 Jan 11. PMID:22136469 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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