PMID- 10365964
OWN - NLM
STAT- MEDLINE
DCOM- 19990624
LR  - 20131121
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 399
IP  - 6735
DP  - 1999 Jun 3
TI  - Structure and ligand of a histone acetyltransferase bromodomain.
PG  - 491-6
AB  - Histone acetylation is important in chromatin remodelling and gene activation.
      Nearly all known histone-acetyltransferase (HAT)-associated transcriptional
      co-activators contain bromodomains, which are approximately 110-amino-acid
      modules found in many chromatin-associated proteins. Despite the wide occurrence 
      of these bromodomains, their three-dimensional structure and binding partners
      remain unknown. Here we report the solution structure of the bromodomain of the
      HAT co-activator P/CAF (p300/CBP-associated factor). The structure reveals an
      unusual left-handed up-and-down four-helix bundle. In addition, we show by a
      combination of structural and site-directed mutagenesis studies that bromodomains
      can interact specifically with acetylated lysine, making them the first known
      protein modules to do so. The nature of the recognition of acetyl-lysine by the
      P/CAF bromodomain is similar to that of acetyl-CoA by histone acetyltransferase. 
      Thus, the bromodomain is functionally linked to the HAT activity of co-activators
      in the regulation of gene transcription.
FAU - Dhalluin, C
AU  - Dhalluin C
AD  - Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai 
      School of Medicine, New York, New York 10029-6574, USA.
FAU - Carlson, J E
AU  - Carlson JE
FAU - Zeng, L
AU  - Zeng L
FAU - He, C
AU  - He C
FAU - Aggarwal, A K
AU  - Aggarwal AK
FAU - Zhou, M M
AU  - Zhou MM
LA  - eng
SI  - PDB/1B91
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Bromine Compounds)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Ligands)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.3.1.- (Acetyltransferases)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (p300-CBP Transcription Factors)
RN  - EC 2.3.1.48 (p300-CBP-associated factor)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Acetyltransferases/chemistry/genetics/*metabolism
MH  - Amino Acid Sequence
MH  - Bromine Compounds/chemistry/*metabolism
MH  - Cell Cycle Proteins/chemistry/*metabolism
MH  - Crystallography, X-Ray
MH  - Escherichia coli
MH  - Histone Acetyltransferases
MH  - Ligands
MH  - Lysine/metabolism
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Protein Binding
MH  - Protein Conformation
MH  - Recombinant Proteins/chemistry/metabolism
MH  - *Saccharomyces cerevisiae Proteins
MH  - Sequence Homology, Amino Acid
MH  - Transcription Factors
MH  - p300-CBP Transcription Factors
EDAT- 1999/06/12 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/06/12 10:00
PHST- 1999/06/12 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/06/12 10:00 [entrez]
AID - 10.1038/20974 [doi]
PST - ppublish
SO  - Nature. 1999 Jun 3;399(6735):491-6. doi: 10.1038/20974.