5ENG

Crystal structure of the bromodomain of human CREBBP in complex with UP39

Summary for 5ENG

• Entry DOI: 10.2210/pdb5eng/pdb
• Descriptor: CREB-binding protein, methyl 2-[2-(3,5-dihydro-2~{H}-pyrazin-4-yl)ethoxy]-5-[(5-ethanoyl-2-ethoxy-phenyl)carbamoyl]benzoate (3 entities in total)
• Functional Keywords: transcription, inhibitor, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 14690.86

Authors

Dong, J.,Caflisch, A. (deposition date: 2015-11-09, release date: 2016-11-23, Last modification date: 2024-01-10)

Primary citation

Zhu, J.,Dong, J.,Batiste, L.,Unzue, A.,Dolbois, A.,Pascanu, V.,Sledz, P.,Nevado, C.,Caflisch, A.
Binding Motifs in the CBP Bromodomain: An Analysis of 20 Crystal Structures of Complexes with Small Molecules.
ACS Med Chem Lett, 9:929-934, 2018

PubMed Abstract: We analyze 20 crystal structures of complexes between the CBP bromodomain and small-molecule ligands that belong to eight different chemotypes identified by docking. The binding motif of the moiety that mimics the natural ligand (acetylated side chain of lysine) at the bottom of the binding pocket is conserved. In stark contrast, the rest of the ligands form different interactions with different side chains and backbone polar groups on the outer rim of the binding pocket. Hydrogen bonds are direct or water-bridged. van der Waals contacts are optimized by rotations of hydrophobic side chains and a slight inward displacement of the ZA loop. Rare types of interactions are observed for some of the ligands.

PubMed: 30258543
DOI: 10.1021/acsmedchemlett.8b00286

Experimental method

X-RAY DIFFRACTION (1.3 Å)