PDBsum entry 4ouf

Transferase

PDB id: 4ouf

Contents

Protein chains

114 a.a.

Ligands

PEG

EDO ×4

Waters ×360

PDB id:

4ouf

Name:

Transferase

Title:

Crystal structure of cbp bromodomain

Structure:

Creb-binding protein. Chain: a, b. Fragment: bromo domain: residues 1082-1197. Engineered: yes

Source:

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

Resolution:

1.40Å R-factor: 0.151 R-free: 0.191

Authors:

S.Roy,C.Das,J.K.Tyler,T.G.Kutateladze

Key ref:

C.Das et al. (2014). Binding of the histone chaperone ASF1 to the CBP bromodomain promotes histone acetylation. Proc Natl Acad Sci U S A, 111, E1072. PubMed id: 24616510 DOI: 10.1073/pnas.1319122111

Date:

17-Feb-14 Release date: 12-Mar-14

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: 10.1073/pnas.1319122111

Proc Natl Acad Sci U S A 111:E1072 (2014)

PubMed id: 24616510

Binding of the histone chaperone ASF1 to the CBP bromodomain promotes histone acetylation.

C.Das, S.Roy, S.Namjoshi, C.S.Malarkey, D.N.Jones, T.G.Kutateladze, M.E.Churchill, J.K.Tyler.

ABSTRACT

The multifunctional Creb-binding protein (CBP) protein plays a pivotal role in many critical cellular processes. Here we demonstrate that the bromodomain of CBP binds to histone H3 acetylated on lysine 56 (K56Ac) with higher affinity than to its other monoacetylated binding partners. We show that autoacetylation of CBP is critical for the bromodomain-H3 K56Ac interaction, and we propose that this interaction occurs via autoacetylation-induced conformation changes in CBP. Unexpectedly, the bromodomain promotes acetylation of H3 K56 on free histones. The CBP bromodomain also interacts with the histone chaperone anti-silencing function 1 (ASF1) via a nearby but distinct interface. This interaction is necessary for ASF1 to promote acetylation of H3 K56 by CBP, indicating that the ASF1-bromodomain interaction physically delivers the histones to the histone acetyl transferase domain of CBP. A CBP bromodomain mutation manifested in Rubinstein-Taybi syndrome has compromised binding to both H3 K56Ac and ASF1, suggesting that these interactions are important for the normal function of CBP.