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PDBsum entry 4xub
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Transcription
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PDB id
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4xub
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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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Crystal structure of the bromodomain of human baz2b in complex with baz2-icr chemical probe
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Structure:
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Bromodomain adjacent to zinc finger domain protein 2b. Chain: a. Fragment: unp residues 1858-1972. Synonym: hwalp4. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: baz2b, kiaa1476. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: r3.
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Resolution:
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1.98Å
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R-factor:
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0.182
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R-free:
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0.215
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Authors:
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A.Chaikuad,I.Felletar,F.Von Delft,C.H.Arrowsmith,A.M.Edwards, C.Bountra,S.Knapp,Structural Genomics Consortium (Sgc)
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Key ref:
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L.Drouin
et al.
(2015).
Structure enabled design of BAZ2-ICR, a chemical probe targeting the bromodomains of BAZ2A and BAZ2B.
J Med Chem,
58,
2553-2559.
PubMed id:
DOI:
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Date:
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25-Jan-15
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Release date:
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11-Mar-15
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PROCHECK
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Headers
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References
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Q9UIF8
(BAZ2B_HUMAN) -
Bromodomain adjacent to zinc finger domain protein 2B from Homo sapiens
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Seq:
Struc:
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2168 a.a.
116 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 2 residue positions (black
crosses)
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DOI no:
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J Med Chem
58:2553-2559
(2015)
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PubMed id:
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Structure enabled design of BAZ2-ICR, a chemical probe targeting the bromodomains of BAZ2A and BAZ2B.
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L.Drouin,
S.McGrath,
L.R.Vidler,
A.Chaikuad,
O.Monteiro,
C.Tallant,
M.Philpott,
C.Rogers,
O.Fedorov,
M.Liu,
W.Akhtar,
A.Hayes,
F.Raynaud,
S.Müller,
S.Knapp,
S.Hoelder.
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ABSTRACT
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The bromodomain containing proteins BAZ2A/B play essential roles in chromatin
remodeling and regulation of noncoding RNAs. We present the structure based
discovery of a potent, selective, and cell active inhibitor 13 (BAZ2-ICR) of the
BAZ2A/B bromodomains through rapid optimization of a weakly potent starting
point. A key feature of the presented inhibitors is an intramolecular aromatic
stacking interaction that efficiently occupies the shallow bromodomain pockets.
13 represents an excellent chemical probe for functional studies of the BAZ2
bromodomains in vitro and in vivo.
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