6v14

Crystal structure of the bromodomain of human BRD9 bound to TP472

spinqualitylabelsall models 6v14, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6v14 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: EDO, QMG Gene: BRD9, UNQ3040/PRO9856 (HUMAN) 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 Inhibition of the bromodomain containing protein 9 (BRD9) by small molecules is an attractive strategy to target mutated SWI/SNF chromatin-remodeling complexes in cancer. However, reported BRD9 inhibitors also inhibit the closely related bromodomain-containing protein 7 (BRD7), which has different biological functions. The structural basis for differential potency and selectivity of BRD9 inhibitors is largely unknown because of the lack of structural information on BRD7. Here, we biochemically and structurally characterized diverse inhibitors with varying degrees of potency and selectivity for BRD9 over BRD7. Novel cocrystal structures of BRD7 liganded with new and previously reported inhibitors of five different chemical scaffolds were determined alongside BRD9 and BRD4. We also report the discovery of first-in-class dual bromodomain-kinase inhibitors outside the bromodomain and extraterminal family targeting BRD7 and BRD9. Combined, the data provide a new framework for the development of BRD7/9 inhibitors with improved selectivity or additional polypharmacologic properties. Structural Basis of Inhibitor Selectivity in the BRD7/9 Subfamily of Bromodomains.,Karim RM, Chan A, Zhu JY, Schonbrunn E J Med Chem. 2020 Mar 6. doi: 10.1021/acs.jmedchem.9b01980. PMID:32091206 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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