5FE2

Crystal structure of human PCAF bromodomain in complex with fragment BR013 (fragment 3)

Summary for 5FE2

• Entry DOI: 10.2210/pdb5fe2/pdb
• Descriptor: Histone acetyltransferase KAT2B, 2-methyl-3~{H}-isoindol-1-one, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: signaling protein, bromodomain, histone acetyltransferase kat2b, histone, acetylation, acetyllysine, epigenetics, structural genomics consortium (sgc)
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : Q92831
• Total number of polymer chains: 2
• Total formula weight: 28887.36

Authors

Chaikuad, A.,von Delft, F.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2015-12-16, release date: 2016-01-13, Last modification date: 2024-01-10)

Primary citation

Chaikuad, A.,Lang, S.,Brennan, P.E.,Temperini, C.,Fedorov, O.,Hollander, J.,Nachane, R.,Abell, C.,Muller, S.,Siegal, G.,Knapp, S.
Structure-Based Identification of Inhibitory Fragments Targeting the p300/CBP-Associated Factor Bromodomain.
J.Med.Chem., 59:1648-1653, 2016

PubMed Abstract: The P300/CBP-associated factor plays a central role in retroviral infection and cancer development, and the C-terminal bromodomain provides an opportunity for selective targeting. Here, we report several new classes of acetyl-lysine mimetic ligands ranging from mM to low micromolar affinity that were identified using fragment screening approaches. The binding modes of the most attractive fragments were determined using high resolution crystal structures providing chemical starting points and structural models for the development of potent and selective PCAF inhibitors.

PubMed: 26731131
DOI: 10.1021/acs.jmedchem.5b01719

Experimental method

X-RAY DIFFRACTION (2.25 Å)