A ligand‐induced conformational change in the yersinia protein tyrosine phosphatase

@article{Schubert1995ALC,
  title={A ligand‐induced conformational change in the yersinia protein tyrosine phosphatase},
  author={Heidi L. Schubert and Eric B. Fauman and Jeanne A. Stuckey and Jack E. Dixon and Mark A. Saper},
  journal={Protein Science},
  year={1995},
  volume={4}
}
Protein tyrosine phosphatases (PTPases) play critical roles in the intracellular signal transduction pathways that regulate cell transformation, growth, and proliferation. The structures of several different PTPases have revealed a conserved active site architecture in which a phosphate‐binding loop, together with an invariant arginine, cradle the phosphate of a phosphotyrosine substrate and poise it for nucleophilic attack by an invariant cysteine nucleophile. We previously reported that… 
Altering the Nucleophile Specificity of a Protein-tyrosine Phosphatase-catalyzed Reaction
TLDR
The conserved Gln-446 residue is responsible for maintaining PTPase’ strict hydrolytic activity and for preventing the PTPases from acting as kinases to phosphorylate undesirable substrates.
Dynamics of the WPD loop of the Yersinia protein tyrosine phosphatase.
TLDR
Simulation results shed light on the role of the WPD loop in PTPase-mediated catalysis, and are useful in structure-based design for novel, selective YopH inhibitors as antibacterial drugs.
Insights into the Reaction of Protein-tyrosine Phosphatase 1B
TLDR
Crystal structures for the transition state analogs for both catalytic steps of protein-tyrosine phosphatase 1B and apo-PTP1B are solved and detailed interactions between the flanking peptide and the enzyme are discussed.
Protein-tyrosine phosphatases: biological function, structural characteristics, and mechanism of catalysis.
  • Z. Zhang
  • Biology, Chemistry
    Critical reviews in biochemistry and molecular biology
  • 1998
TLDR
Biochemical experiments demonstrate that phosphatases in the PTPase superfamily utilize a common mechanism for catalysis going through a covalent thiophosphate intermediate that involves the nucleophilic Cys residue in thePTPase signature motif.
Loop dynamics and ligand binding kinetics in the reaction catalyzed by the Yersinia protein tyrosine phosphatase.
TLDR
The dynamics associated with substrate binding in YopH have been determined and results indicate that substrate binding is coupled to the W PD loop motion, and WPD loop dynamics occur in the sub-millisecond time scale.
Molecular Basis for Substrate Specificity of Protein-tyrosine Phosphatase 1B*
Protein-tyrosine phosphatases can exhibit stringent substrate specificity in vivo, although the molecular basis for this is not well understood. The three-dimensional structure of the catalytically
The structure of apo protein‐tyrosine phosphatase 1B C215S mutant: More than just an S → O change
TLDR
The structure of the apo‐PTP1B C215S mutant is reported, which reveals that, while the WPD loop is in the open conformation observed in the Apo WT enzyme crystal structure, the residues of the PTPases signature motif are in a dramatically different conformation.
The X-ray Crystal Structures of Yersinia Tyrosine Phosphatase with Bound Tungstate and Nitrate
TLDR
X-ray crystal structures of the Yersinia tyrosine phosphatase in complex with tungstate and nitrate have been solved to 2.4-Å resolution and are consistent with a general acid-catalyzed, in-line displacement of the phosphate moiety to Cys403 on the enzyme, followed by attack by a nucleophilic water molecule to release orthophosphate.
Probing the function of the conserved tryptophan in the flexible loop of the Yersinia protein-tyrosine phosphatase.
TLDR
Results indicate that Trp354 is an important residue that keeps the WpD loop in a catalytically competent conformation and positions the general acid/base Asp356 in the correct orientation for proton transfer.
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References

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PROTEIN tyrosine phosphatases (PTPases) and kinases coregulate the critical levels of phosphorylation necessary for intracellular signalling, cell growth and differentiation1,2. Yersinia, the
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TLDR
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