5lvq

Crystal structure of human PCAF bromodomain in complex with compound-D (CPD-D), N-methyl-2-(tetrahydro-2H-pyran-4-yloxy)benzamideCrystal structure of human PCAF bromodomain in complex with compound-D (CPD-D), N-methyl-2-(tetrahydro-2H-pyran-4-yloxy)benzamide

Structural highlights 5lvq 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. Method: X-ray diffraction, Resolution 2.05Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KAT2B_HUMAN Functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles. Also acetylates non-histone proteins, such as ACLY. Inhibits cell-cycle progression and counteracts the mitogenic activity of the adenoviral oncoprotein E1A. In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. Publication Abstract from PubMed The discovery of novel bromodomain inhibitors by fragment screening is complicated by the presence of dimethyl sulfoxide (DMSO), an acetyl-lysine mimetic, that can compromise the detection of low affinity fragments. We demonstrate surface plasmon resonance as a primary fragment screening approach for the discovery of novel bromodomain scaffolds, by describing a protocol to overcome the DMSO interference issue. We describe the discovery of several novel small molecules scaffolds that inhibit the bromodomains PCAF, BRD4, and CREBBP, representing canonical members of three out of the seven subfamilies of bromodomains. High-resolution crystal structures of the complexes of key fragments binding to BRD4(1), CREBBP, and PCAF were determined to provide binding mode data to aid the development of potent and selective inhibitors of PCAF, CREBBP, and BRD4. Discovery of New Bromodomain Scaffolds by Biosensor Fragment Screening.,Navratilova I, Aristotelous T, Picaud S, Chaikuad A, Knapp S, Filappakopoulos P, Hopkins AL ACS Med Chem Lett. 2016 Sep 20;7(12):1213-1218. eCollection 2016 Dec 8. PMID:27994766 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone acetyltransferase 3D structures

spinqualitylabelsall models 5lvq, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image