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PDBsum entry 4nra
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Transcription
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PDB id
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4nra
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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 compound-6 e11322
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Structure:
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Bromodomain adjacent to zinc finger domain protein 2b. Chain: a. Fragment: bromodomain (unp residues 2054-2168). 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.
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Resolution:
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1.85Å
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R-factor:
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0.179
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R-free:
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0.212
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Authors:
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A.Chaikuad,I.Felletar,F.M.Ferguson,P.Filippakopoulos,O.Fedorov,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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F.M.Ferguson
et al.
(2013).
Targeting low-druggability bromodomains: fragment based screening and inhibitor design against the BAZ2B bromodomain.
J Med Chem,
56,
10183-10187.
PubMed id:
DOI:
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Date:
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26-Nov-13
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Release date:
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25-Dec-13
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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
56:10183-10187
(2013)
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PubMed id:
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Targeting low-druggability bromodomains: fragment based screening and inhibitor design against the BAZ2B bromodomain.
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F.M.Ferguson,
O.Fedorov,
A.Chaikuad,
M.Philpott,
J.R.Muniz,
I.Felletar,
F.von Delft,
T.Heightman,
S.Knapp,
C.Abell,
A.Ciulli.
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ABSTRACT
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Bromodomains are epigenetic reader domains that have recently become popular
targets. In contrast to BET bromodomains, which have proven druggable,
bromodomains from other regions of the phylogenetic tree have shallower pockets.
We describe successful targeting of the challenging BAZ2B bromodomain using
biophysical fragment screening and structure-based optimization of high
ligand-efficiency fragments into a novel series of low-micromolar inhibitors.
Our results provide attractive leads for development of BAZ2B chemical probes
and indicate the whole family may be tractable.
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Links
