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PDBsum entry 4nrc

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protein ligands links
Transcription PDB id
4nrc
Jmol PyMol
Contents
Protein chain
115 a.a.
Ligands
2LY
EDO ×2
15P
Waters ×231
PDB id:
4nrc
Name: Transcription
Title: Crystal structure of the bromodomain of human baz2b in compl compound-3 n01186
Structure: Bromodomain adjacent to zinc finger domain protei chain: a. Fragment: bromodomain (unp residues 2054-2168). Synonym: hwalp4. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: baz2b, kiaa1476. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Resolution:
1.86Å     R-factor:   0.173     R-free:   0.191
Authors: J.R.C.Muniz,I.Felletar,A.Chaikuad,P.Filippakopoulos,F.M.Ferg O.Fedorov,F.Von Delft,C.H.Arrowsmith,A.M.Edwards,C.Bountra, S.Knapp,Structural Genomics Consortium (Sgc)
Key ref: 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: 24304323 DOI: 10.1021/jm401582c
Date:
26-Nov-13     Release date:   25-Dec-13    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9UIF8  (BAZ2B_HUMAN) -  Bromodomain adjacent to zinc finger domain protein 2B
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
2168 a.a.
115 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 

 
DOI no: 10.1021/jm401582c J Med Chem 56:10183-10187 (2013)
PubMed id: 24304323  
 
 
Targeting low-druggability bromodomains: fragment based screening and inhibitor design against the BAZ2B bromodomain.
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.
 
  ABSTRACT  
 
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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