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

  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},
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
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.
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
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
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.
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
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
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.
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.


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
Dissecting the catalytic mechanism of protein-tyrosine phosphatases.
  • Z. Zhang, Y. Wang, J. Dixon
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1994
The results suggest that all PTP-ases use a common mechanism that depends upon formation of a thiol-phosphate intermediate and general acid-general base catalysis.
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 crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase
The structure of the low-molecular-weight PTPase supports a reaction mechanism involving the conserved Cys 12 as an attacking nucleophile in an in-line associative mechanism and suggests a catalytic role for Asp 129 in the reaction cycle.
Active site labeling of the Yersinia protein tyrosine phosphatase: the determination of the pKa of the active site cysteine and the function of the conserved histidine 402.
It is demonstrated that the Yersinia protein tyrosine phosphatase (PTPase) could be inactivated by the alkylating agent iodoacetate, and the residue that was labeled by iodo acetate was shown to be Cys403, which was the same catalytically essential residue identified by site-directed mutagenesis.
The Cys(X)5Arg catalytic motif in phosphoester hydrolysis.
It is shown that Arg409 plays a critical role in PTPase action and that the Cys(X)5Arg active site motif forms a phosphate-binding loop which appears to represent the essential features necessary for catalysis by the PTPases, the dual specific phosphatase, and the low molecular weight acid phosphatases.
Protein tyrosine phosphatases: a diverse family of intracellular and transmembrane enzymes.
A hypothesis is proposed explaining how phosphatases might act synergistically with the kinases to elicit a full physiological response, without regard to the state of phosphorylation of the target proteins.
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