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PDBsum entry 4ifi

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Transcription PDB id
4ifi
Jmol PyMol
Contents
Protein chain
211 a.a.
Ligands
ARG-SEP-PRO-VAL-
PHE-SER
ACT
Waters ×66
PDB id:
4ifi
Name: Transcription
Title: Structure of human brca1 brct in complex with baat peptide
Structure: Breast cancer type 1 susceptibility protein. Chain: a. Fragment: brct domain, unp residues 1650-1859. Synonym: ring finger protein 53. Engineered: yes. Baat peptide. Chain: b. Fragment: unp residues 268-273. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: brca1, rnf53. Expressed in: escherichia coli. Expression_system_taxid: 511693. Synthetic: yes. Other_details: the sequence occurs naturally in humans
Resolution:
2.20Å     R-factor:   0.200     R-free:   0.261
Authors: X.Liu,J.A.A.Ladias
Key ref: X.Liu and J.A.Ladias (2013). Structural basis for the BRCA1 BRCT interaction with the proteins ATRIP and BAAT1. Biochemistry, 52, 7618-7627. PubMed id: 24073851 DOI: 10.1021/bi400714v
Date:
14-Dec-12     Release date:   30-Oct-13    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P38398  (BRCA1_HUMAN) -  Breast cancer type 1 susceptibility protein
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1863 a.a.
211 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.3.2.27  - RING-type E3 ubiquitin transferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6- ubiquitinyl-[acceptor protein]-L-lysine
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     response to DNA damage stimulus   2 terms 
  Biochemical function     DNA binding     3 terms  

 

 
DOI no: 10.1021/bi400714v Biochemistry 52:7618-7627 (2013)
PubMed id: 24073851  
 
 
Structural basis for the BRCA1 BRCT interaction with the proteins ATRIP and BAAT1.
X.Liu, J.A.Ladias.
 
  ABSTRACT  
 
The breast and ovarian cancer susceptibility protein 1 (BRCA1) plays a central role in DNA damage response (DDR). Two tandem BRCA1 C-terminal (BRCT) domains interact with several proteins that function in DDR and contain the generally accepted motif pS-X-X-F (pS denoting phosphoserine and X any amino acid), including the ATR-interacting protein (ATRIP) and the BRCA1-associated protein required for ATM activation-1 (BAAT1). The crystal structures of the BRCA1 BRCTs bound to the phosphopeptides ATRIP (235-PEACpSPQFG-243) and BAAT1 (266-VARpSPVFSS-274) were determined at 1.75 Å and 2.2 Å resolution, respectively. The pSer and Phe(+3) anchor the phosphopeptides into the BRCT binding groove, with adjacent peptide residues contributing to the interaction. In the BRCA1-ATRIP structure, Gln(+2) is accommodated through a conformational change of the BRCA1 E1698 side chain. Importantly, isothermal titration calorimetry experiments showed that the size and charge of the side chains at peptide positions +1 and +2 contribute significantly to the BRCA1 BRCT-peptide binding affinity. In particular, the Asp(+1) and Glu(+2) in the human CDC27 peptide 816-HAAEpSDEF-823 abrogate the interaction with the BRCA1 BRCTs due in large part to electrostatic repulsion between Glu(+2) and E1698, indicating a preference of these domains for specific side chains at positions +1 and +2. These results emphasize the need for a systematic assessment of the contribution of the peptide residues surrounding pSer and Phe(+3) to the binding affinity and specificity of the BRCA1 BRCTs in order to elucidate the molecular mechanisms underlying the hierarchy of target selection by these versatile domains during DDR and tumorigenesis.
 

 

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