PDBsum entry 5dbm

Protein binding

PDB id: 5dbm

Contents

Protein chains

114 a.a.

Ligands

58N ×3

Waters ×355

PDB id:

5dbm

Name:

Protein binding

Title:

Crystal structure of the cbp bromodomain in complex with cpi703

Structure:

Creb-binding protein. Chain: a, b, c. Fragment: bromodomain (unp residues 1082-1197). Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: crebbp, cbp. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.86Å R-factor: 0.175 R-free: 0.220

Authors:

J.W.Setser,F.Poy,S.F.Bellon

Key ref:

S.Ghosh et al. (2016). Regulatory T Cell Modulation by CBP/EP300 Bromodomain Inhibition. J Biol Chem, 291, 13014-13027. PubMed id: 27056325 DOI: 10.1074/jbc.M115.708560

Date:

21-Aug-15 Release date: 20-Apr-16

Protein chains

Q92793  (CBP_HUMAN) -  CREB-binding protein from Homo sapiens

Seq: 2442 a.a.

Struc: 114 a.a.

Enzyme reactions

• Enzyme class 1: E.C.2.3.1.- - ?????
• Enzyme class 2: E.C.2.3.1.48 - histone acetyltransferase.
• Reaction: L-lysyl-[protein] + acetyl-CoA = N₆-acetyl-L-lysyl-[protein] + CoA + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1074/jbc.M115.708560

J Biol Chem 291:13014-13027 (2016)

PubMed id: 27056325

Regulatory T Cell Modulation by CBP/EP300 Bromodomain Inhibition.

S.Ghosh, A.Taylor, M.Chin, H.R.Huang, A.R.Conery, J.A.Mertz, A.Salmeron, P.J.Dakle, D.Mele, A.Cote, H.Jayaram, J.W.Setser, F.Poy, G.Hatzivassiliou, D.DeAlmeida-Nagata, P.Sandy, C.Hatton, F.A.Romero, E.Chiang, T.Reimer, T.Crawford, E.Pardo, V.G.Watson, V.Tsui, A.G.Cochran, L.Zawadzke, J.C.Harmange, J.E.Audia, B.M.Bryant, R.T.Cummings, S.R.Magnuson, J.L.Grogan, S.F.Bellon, B.K.Albrecht, R.J.Sims, J.M.Lora.

ABSTRACT

Covalent modification of histones is a fundamental mechanism of regulated gene expression in eukaryotes, and interpretation of histone modifications is an essential feature of epigenetic control. Bromodomains are specialized binding modules that interact with acetylated histones, linking chromatin recognition to gene transcription. Because of their ability to function in a domain-specific fashion, selective disruption of bromodomain:acetylated histone interactions with chemical probes serves as a powerful means for understanding biological processes regulated by these chromatin adaptors. Here we describe the discovery and characterization of potent and selective small molecule inhibitors for the bromodomains of CREBBP/EP300 that engage their target in cellular assays. We use these tools to demonstrate a critical role for CREBBP/EP300 bromodomains in regulatory T cell biology. Because regulatory T cell recruitment to tumors is a major mechanism of immune evasion by cancer cells, our data highlight the importance of CREBBP/EP300 bromodomain inhibition as a novel, small molecule-based approach for cancer immunotherapy.