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PDBsum entry 2dvr
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Transcription
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PDB id
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2dvr
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Contents |
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* Residue conservation analysis
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PDB id:
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Transcription
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Title:
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Crystal structure analysis of the n-terminal bromodomain of human brd2 complexed with acetylated histone h4 peptide
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Structure:
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Bromodomain-containing protein 2. Chain: a, b, c. Fragment: n-terminal bromodomain, bd1. Synonym: ring3 protein, o27.1.1. Engineered: yes. Histone h4. Chain: p, q. Fragment: n-term tail. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: expressed by cell-free system. Synthetic: yes. Other_details: synthetic peptide
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Resolution:
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2.30Å
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R-factor:
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0.182
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R-free:
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0.243
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Authors:
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Y.Nakamura,T.Umehara,M.Shirouzu,B.Padmanabhan,S.Yokoyama,Riken Structural Genomics/proteomics Initiative (Rsgi)
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Key ref:
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T.Umehara
et al.
(2010).
Structural basis for acetylated histone H4 recognition by the human BRD2 bromodomain.
J Biol Chem,
285,
7610-7618.
PubMed id:
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Date:
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01-Aug-06
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Release date:
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07-Aug-07
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PROCHECK
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Headers
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References
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J Biol Chem
285:7610-7618
(2010)
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PubMed id:
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Structural basis for acetylated histone H4 recognition by the human BRD2 bromodomain.
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T.Umehara,
Y.Nakamura,
M.K.Jang,
K.Nakano,
A.Tanaka,
K.Ozato,
B.Padmanabhan,
S.Yokoyama.
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ABSTRACT
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Recognition of acetylated chromatin by the bromodomains and extra-terminal
domain (BET) family proteins is a hallmark for transcriptional activation and
anchoring viral genomes to mitotic chromosomes of the host. One of the BET
family proteins BRD2 interacts with acetylated chromatin during mitosis and
leads to transcriptional activation in culture cells. Here, we report the
crystal structures of the N-terminal bromodomain of human BRD2 (BRD2-BD1;
residues 74-194) in complex with each of three different Lys-12-acetylated H4
peptides. The BRD2-BD1 recognizes the H4 tail acetylated at Lys-12 (H4K12ac),
whereas the side chain of hypoacetylated Lys-8 of H4 binds at the cavity of the
dimer interface of BRD2-BD1. From binding studies, we identified the BRD2-BD1
residues that are responsible for recognition of the Lys-12-acetylated H4 tail.
In addition, mutation to Lys-8 in the Lys-12-acetylated H4 tail decreased the
binding to BRD2-BD1, implicating the critical role of Lys-8 in the
Lys-12-acetylated H4 tail for the recognition by BRD2-BD1. Our findings provide
a structural basis for deciphering the histone code by the BET bromodomain
through the binding with a long segment of the histone H4 tail, which presumably
prevents erasure of the histone code during the cell cycle.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.C.Belkina,
and
G.V.Denis
(2012).
BET domain co-regulators in obesity, inflammation and cancer.
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Nat Rev Cancer,
12,
465-477.
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R.Zhao,
T.Nakamura,
Y.Fu,
Z.Lazar,
and
D.L.Spector
(2011).
Gene bookmarking accelerates the kinetics of post-mitotic transcriptional re-activation.
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Nat Cell Biol,
13,
1295-1304.
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T.Ito,
T.Umehara,
K.Sasaki,
Y.Nakamura,
N.Nishino,
T.Terada,
M.Shirouzu,
B.Padmanabhan,
S.Yokoyama,
A.Ito,
and
M.Yoshida
(2011).
Real-time imaging of histone H4K12-specific acetylation determines the modes of action of histone deacetylase and bromodomain inhibitors.
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Chem Biol,
18,
495-507.
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
