Binding motifs in the CBP Bromodomain: an analysis of 20 crystal structures of complexes with small molecules

TitleBinding motifs in the CBP Bromodomain: an analysis of 20 crystal structures of complexes with small molecules
Publication TypeJournal Article
Year of Publication2018
AuthorsZhu J., Dong J., Batiste L., Unzue A., Dolbois A., Pascanu V., Śledź P., Nevado C., Caflisch A.
JournalACS Med Chem Lett
Volume9
Issue9
Pagination929-934
Date Published2018 Sep 13
Type of ArticleResearch Article
ISSN1948-5875
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.

DOI10.1021/acsmedchemlett.8b00286
pubindex

0240

Alternate JournalACS Med. Chem. Lett.
PubMed ID30258543
PubMed Central IDPMC6142054