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PDBsum entry 4uiy
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Transcription
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PDB id
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4uiy
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PDB id:
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| Name: |
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Transcription
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Title:
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N-terminal bromodomain of human brd4 with n-(1,1-dioxo-1-thian-4-yl)- 5-methyl-4-oxo-7-3-(trifluoromethyl)phenyl-4h,5h-thieno-3,2-c- pyridine-2-carboximidamide
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Structure:
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Bromodomain-containing protein 4. Chain: a. Fragment: n-terminal bromodomain, residues 44-168. Synonym: protein hunk1, human brd4. 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
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Resolution:
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1.30Å
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R-factor:
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0.158
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R-free:
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0.185
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Authors:
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C.Chung,N.T.Theodoulou,P.Bamborough,P.G.Humphreys
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Key ref:
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N.H.Theodoulou
et al.
(2016).
Discovery of I-BRD9, a Selective Cell Active Chemical Probe for Bromodomain Containing Protein 9 Inhibition.
J Med Chem,
59,
1425-1439.
PubMed id:
DOI:
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Date:
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03-Apr-15
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Release date:
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22-Apr-15
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PROCHECK
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Headers
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References
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O60885
(BRD4_HUMAN) -
Bromodomain-containing protein 4 from Homo sapiens
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Seq:
Struc:
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1362 a.a.
127 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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DOI no:
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J Med Chem
59:1425-1439
(2016)
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PubMed id:
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Discovery of I-BRD9, a Selective Cell Active Chemical Probe for Bromodomain Containing Protein 9 Inhibition.
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N.H.Theodoulou,
P.Bamborough,
A.J.Bannister,
I.Becher,
R.A.Bit,
K.H.Che,
C.W.Chung,
A.Dittmann,
G.Drewes,
D.H.Drewry,
L.Gordon,
P.Grandi,
M.Leveridge,
M.Lindon,
A.M.Michon,
J.Molnar,
S.C.Robson,
N.C.Tomkinson,
T.Kouzarides,
R.K.Prinjha,
P.G.Humphreys.
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ABSTRACT
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Acetylation of histone lysine residues is one of the most well-studied
post-translational modifications of chromatin, selectively recognized by
bromodomain "reader" modules. Inhibitors of the bromodomain and extra
terminal domain (BET) family of bromodomains have shown profound anticancer and
anti-inflammatory properties, generating much interest in targeting other
bromodomain-containing proteins for disease treatment. Herein, we report the
discovery of I-BRD9, the first selective cellular chemical probe for
bromodomain-containing protein 9 (BRD9). I-BRD9 was identified through
structure-based design, leading to greater than 700-fold selectivity over the
BET family and 200-fold over the highly homologous bromodomain-containing
protein 7 (BRD7). I-BRD9 was used to identify genes regulated by BRD9 in
Kasumi-1 cells involved in oncology and immune response pathways and to the best
of our knowledge, represents the first selective tool compound available to
elucidate the cellular phenotype of BRD9 bromodomain inhibition.
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Links
