5i40

BRD9 in complex with Cpd1 (6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one)

spinqualitylabelsall models 5i40, resolution 1.04Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5i40 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.0402Å Ligands: 67N, EDO, PEG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BRD9_HUMAN May play a role in chromatin remodeling and regulation of transcription. Publication Abstract from PubMed The biological role played by non-BET bromodomains remains poorly understood, and it is therefore imperative to identify potent and highly selective inhibitors to effectively explore the biology of individual bromodomain proteins. A ligand-efficient nonselective bromodomain inhibitor was identified from a 6-methyl pyrrolopyridone fragment. Small hydrophobic substituents replacing the N-methyl group were designed directing toward the conserved bromodomain water pocket, and two distinct binding conformations were then observed. The substituents either directly displaced and rearranged the conserved solvent network, as in BRD4(1) and TAF1(2), or induced a narrow hydrophobic channel adjacent to the lipophilic shelf, as in BRD9 and CECR2. The preference of distinct substituents for individual bromodomains provided selectivity handles useful for future lead optimization efforts for selective BRD9, CECR2, and TAF1(2) inhibitors. Diving into the Water: Inducible Binding Conformations for BRD4, TAF1(2), BRD9, and CECR2 Bromodomains.,Crawford TD, Tsui V, Flynn EM, Wang S, Taylor AM, Cote A, Audia JE, Beresini MH, Burdick DJ, Cummings R, Dakin LA, Duplessis M, Good AC, Hewitt MC, Huang HR, Jayaram H, Kiefer JR, Jiang Y, Murray J, Nasveschuk CG, Pardo E, Poy F, Romero FA, Tang Y, Wang J, Xu Z, Zawadzke LE, Zhu X, Albrecht BK, Magnuson SR, Bellon S, Cochran AG J Med Chem. 2016 Jun 9;59(11):5391-402. doi: 10.1021/acs.jmedchem.6b00264. Epub, 2016 May 31. PMID:27219867 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Bromodomain-containing protein 3D structures

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