5l97 | pdb_00005l97

Crystal Structure of BAZ2B bromodomain in complex with 3-amino-2-methylpyridine derivative 3

spinqualitylabelsall models 5l97, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5l97 is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 6RW Related: 5e9k, 5l8t, 5l8u, 5l96 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [BAZ2B_HUMAN] May play a role in transcriptional regulation interacting with ISWI. Publication Abstract from PubMed The 3-amino-2-methylpyridine derivative 1 was identified as ligand of the BAZ2B bromodomain by automatic docking of nearly 500 compounds, selected on the basis of previous fragment hits. Hit expansion by two in silico approaches, pharmacophore search followed by docking, and substructure search resulted in five additional ligands. The predicted binding mode of the six 3-amino-2-methylpyridine derivatives was validated by protein crystallography. A small displacement of residues 1894-1899 of the ZA loop is observed for two of the six ligands. In all structures, the pyridine head is involved in a water-mediated hydrogen bond with the side chain of the conserved Tyr1901 while the 3-amino linker acts as hydrogen bond donor for the backbone carbonyl of Pro1888. Heterogeneous orientations are observed for the tail groups (i.e., the 3-amino substituents). The sulfonyl group in the tail of compounds 1 and 2 is involved in a hydrogen bond with the backbone amide of Asn1894. Derivatives of 3-amino-2-methylpyridine as BAZ2B Bromodomain Ligands: in silico Discovery and in crystallo Validation.,Marchand JR, Lolli G, Caflisch A J Med Chem. 2016 Oct 12. PMID:27731638 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA