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PDBsum entry 3db1

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protein ligands Protein-protein interface(s) links
Hydrolase PDB id
3db1
Jmol
Contents
Protein chains
267 a.a. *
Ligands
PO4 ×3
Waters ×6
* Residue conservation analysis
PDB id:
3db1
Name: Hydrolase
Title: Crystal structure of the 2h-phosphatase domain of sts-2 in c with phosphate
Structure: Sts-2 protein. Chain: a, b, c, d. Fragment: pgm domain. Engineered: yes
Source: Mus musculus. Mouse. Organism_taxid: 10090. Gene: ubash3a. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.77Å     R-factor:   0.247     R-free:   0.270
Authors: N.Nassar,Y.Chen,N.Carpino
Key ref: Y.Chen et al. (2009). Structural and functional characterization of the 2H-phosphatase domain of Sts-2 reveals an acid-dependent phosphatase activity. Biochemistry, 48, 1681-1690. PubMed id: 19196006
Date:
30-May-08     Release date:   03-Mar-09    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q3V3E1  (UBS3A_MOUSE) -  Ubiquitin-associated and SH3 domain-containing protein A
Seq:
Struc:
 
Seq:
Struc:
624 a.a.
267 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 

 
Biochemistry 48:1681-1690 (2009)
PubMed id: 19196006  
 
 
Structural and functional characterization of the 2H-phosphatase domain of Sts-2 reveals an acid-dependent phosphatase activity.
Y.Chen, J.Jakoncic, N.Carpino, N.Nassar.
 
  ABSTRACT  
 
The suppressors of T cell receptor (TCR) signaling 1 and 2 (Sts-1 and -2, respectively) are multidomain proteins that negatively regulate the signaling of membrane-bound receptors, including TCR and the epidermal growth factor receptor (EGFR). Sts-1 was recently shown to be a new type of protein tyrosine phosphatase (PTP), with the phosphatase activity located within its C-terminal phosphoglycerate mutase (PGM) homology domain and key for the regulation of TCR signaling in T cells. The activity of the related Sts-2 enzyme is significantly less than that of Sts-1. Here we investigate the phosphatase activity of the PGM domain of Sts-2, Sts-2(PGM). The crystal structure of Sts-2(PGM) is remarkably similar to Sts-1(PGM), including conservation of all catalytic residues. Insight into mechanistic details is provided by the structures of the apo, tungstate-bound, and phosphate-bound enzyme. The active site shows stringent specificity, with the k(cat) optimum at pH 5.0 suggesting that Sts-2 might function as an acid-dependent phosphatase. Mutation of active site residues Gln372, Ala446, Glu481, Ser552, and Ser582 to their equivalents in Sts-1 increases the phosphatase activity of Sts-2(PGM) toward model substrates. Overall, our data demonstrate that Sts-2(PGM) adopts the conformation of an active phosphatase whose activity is fundamentally different from that of Sts-1 despite the strong structural homology. They also demonstrate that nonconserved active site residues are responsible for the difference in activity between the two isoforms. These differences reflect possible distinct physiological substrates.