Crystal Structure of the Dual Specificity Protein Phosphatase VHR

  title={Crystal Structure of the Dual Specificity Protein Phosphatase VHR},
  author={Jirundon Yuvaniyama and John M. Denu and Jack E. Dixon and Mark A. Saper},
  pages={1328 - 1331}
Dual specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle. Here, the crystal structure of a human DSP, vaccinia H1-related phosphatase (or VHR), was determined at 2.1 angstrom resolution. A shallow active site pocket in VHR allows for the hydrolysis of phosphorylated serine, threonine, or tyrosine protein residues, whereas the deeper active site of protein tyrosine phosphatases (PTPs) restricts substrate specificity to only phosphotyrosine… 
Structure of Human Dual Specificity Protein Phosphatase 23, VHZ, Enzyme-Substrate/Product Complex*
Human VHZ, the smallest of the catalytically active protein-tyrosine phosphatases (PTP) reported to date, is a class I Cys-based PTP and bears the distinctive active site signature motif HCXXGXXRS(T).
Crystal structure of human TMDP, a testis‐specific dual specificity protein phosphatase: Implications for substrate specificity
The crystal structure of human TMDP is reported at a resolution of 2.4 Å, showing distinct structural motifs and surface properties and allowing equal binding of phosphotyrosine and phosphothreonine substrates.
Crystal structure of the catalytic domain of human DUSP5, a dual specificity MAP kinase protein phosphatase
Structural features of DUSP5 indicate that D USP5 has a different mechanism of substrate recognition than other DS-MKPs, which should pave the way for the rational design of specific inhibitors.
Structure of human DSP18, a member of the dual-specificity protein tyrosine phosphatase family.
The crystal structure of human DSP18 has been determined and it is found that the residues at the C-terminus fold into two antiparallel beta-strands and participate in extensive interactions with the catalytic domain, explaining the thermostability of D SP18.
The structure of the cell cycle protein Cdc14 reveals a proline‐directed protein phosphatase
Structural and kinetic data support a role for Cdc14 in the preferential dephosphorylation of proteins modified by proline‐directed kinases.
Crystal structure of the catalytic domain of human VHY, a dual‐specificity protein phosphatase
The detailed structural information of VHYc reveals distinct structural motif and surface properties compared to those of VHR, suggesting that VHY may have unique substrate specificity and a regulation mechanism in the regulation of meiotic signal transduction in testis cells.
Mechanistic studies on protein tyrosine phosphatases.
  • Zhon-Yin Zhang
  • Biology
    Progress in nucleic acid research and molecular biology
  • 2003
Dimeric Quaternary Structure of the Prototypical Dual Specificity Phosphatase VH1*
It is proposed that the dimeric quaternary structure of VH1 is essential for specific recognition of activated STAT1, which prevents its nuclear translocation, thus blocking interferon-γ signal transduction and antiviral response.
Atomic structure of dual-specificity phosphatase 26, a novel p53 phosphatase.
The structural characterization of DUSP26 presented in this paper provides the first atomic insight into this disease-associated phosphatase, and it is proposed that a substrate-induced conformational change, possibly involving rearrangement of helix α9 with respect to theosphatase core, allows D USP26 to adopt a catalytically active conformation.
Peptide recognition and dephosphorylation by the vaccinia VH1 phosphatase
It is proposed that the enzyme-substrate contact residues described here may serve as molecular targets for the development of inhibitors that specifically block VH1 catalytic activity and thus poxvirus replication.


Crystal structure of human protein tyrosine phosphatase 1B.
The structure of PTP1B should serve as a model for other members of the PTP family and as a framework for understanding the mechanism of tyrosine dephosphorylation.
The catalytic role of Cys124 in the dual specificity phosphatase VHR.
Structural basis for phosphotyrosine peptide recognition by protein tyrosine phosphatase 1B.
The crystal structures of a cysteine-215-->serine mutant of protein tyrosine phosphatase 1B complexed with high-affinity peptide substrates corresponding to an autophosphorylation site of the
A Tyr/Ser protein phosphatase encoded by vaccinia virus
The vaccinia virus genome contains an open reading frame which shares amino-acid sequence identity with the PTPases, and mutagenesis of an essential Cys in the vaccinia phosphatase abolishes catalytic activity directed towards both substrates, suggesting that hydrolysis proceeds by a common mechanism.
A ligand‐induced conformational change in the yersinia protein tyrosine phosphatase
It is speculated that the intrinsic loop flexibility of different PTPases may be related to their catalytic rate and may play a role in the wide range of activities observed within this enzyme family.
A catalytic mechanism for the dual-specific phosphatases.
  • J. Denu, J. Dixon
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1995
Results from a previous study suggest that the S131A mutation alters the rate-limiting step in the catalytic mechanism of the dual-specific protein-tyrosine phosphatase VHR, and formation of a phosphoenzyme intermediate appears to be rate- Limiting with the native enzyme.
Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 Å and the complex with tungstate
PROTEIN tyrosine phosphatases (PTPases) and kinases coregulate the critical levels of phosphorylation necessary for intracellular signalling, cell growth and differentiation1,2. Yersinia, the
Visualization of intermediate and transition-state structures in protein-tyrosine phosphatase catalysis.
Kinetic analysis of D92N and D181N mutants indicated that aspartic acid acts as a general acid by protonating the leaving-group phenolic oxygen, and a unifying mechanism for catalysis is proposed.