Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 Å and the complex with tungstate

  title={Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 {\AA} and the complex with tungstate},
  author={Jeanne A. Stuckey and Heidi L. Schubert and Eric B. Fauman and Zhon-Yin Zhang and Jack E. Dixon and Mark A. Saper},
PROTEIN tyrosine phosphatases (PTPases) and kinases coregulate the critical levels of phosphorylation necessary for intracellular signalling, cell growth and differentiation1,2. Yersinia, the causative bacteria of the bubonic plague and other enteric diseases, secrete an active PTPase3, Yop51, that enters and suppresses host immune cells4,5. Though the catalytic domain is only ∼20% identical to human PTP1B6, the Yersinia PTPase contains all of the invariant residues present in eukaryotic… 
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.
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.
Crystal Structure of the Catalytic Domain of Protein-tyrosine Phosphatase SHP-1*
Sequence alignment and structural analysis suggest that the residues in the WPD loop, especially the amino acid following Asp421, are critical for the movement of W PD loop on binding substrates and the specific activity of protein-tyrosine phosphatases.
Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution.
The model presents a framework for understanding not only the classical Mn2+/Mg2+‐dependent protein phosphatases but also the sequence‐related domains of mitochondrial pyruvate dehydrogenase phosphatase, the Bacillus subtilusosphatase SpoIIE and a 300‐residue domain within yeast adenyl cyclase.
Crystal Structure of the Yersinia Protein-tyrosine Phosphatase YopH Complexed with a Specific Small Molecule Inhibitor*
A specific YopH small molecule inhibitor is identified, p-nitrocatechol sulfate (pNCS), which exhibits a Ki value of 25 μm for Yop H and displays a 13–60-fold selectivity in favor of Yoph against a panel of mammalian PTPs.
Identification of Residues in the N-terminal Domain of theYersinia Tyrosine Phosphatase That Are Critical for Substrate Recognition*
The random mutagenesis in combination with the yeast two-hybrid system indicated that the substrate- and SycH-binding activities of the YopH N-terminal domain can be separated and that the former activity is important for recognition and dephosphorylation of substrates by YOpHin vivo.
Crystal Structure of Low-Molecular-Weight Protein Tyrosine Phosphatase from Mycobacterium tuberculosis at 1.9-Å Resolution
The crystal structure of LMWPTPase of microbial origin, the first of its kind from Mycobacterium tuberculosis, is reported, and differences are observed in the residues involved, suggesting that they have a role in influencing different substrate specificities.
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.


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.
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.
Tyrosine phosphate hydrolysis of host proteins by an essential Yersinia virulence determinant.
Observations indicate that the essential function of YopH in Yersinia pathogenesis is host-protein dephosphorylation, suggesting thatYopH is functionally expressed by extracellular bacteria.
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.
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.
Protein tyrosine phosphatase substrate specificity: size and phosphotyrosine positioning requirements in peptide substrates.
It is demonstrated that the thiophosphoryl analog in which one of the phosphate oxygens is replaced by sulfur can be hydrolyzed by PTPases, whereas the phosphonomethylphenylalanine analog is a competitive and nonhydrolyzable inhibitor.
Distinct functional roles of the two intracellular phosphatase like domains of the receptor‐linked protein tyrosine phosphatases LCA and LAR.
It is shown that the first of the two domains has enzyme activity by itself, and that one cysteine residue in the first domain of both LCA and LAR is absolutely required for activity.
Protein tyrosine phosphatase activity of an essential virulence determinant in Yersinia.
Amino acids surrounding an essential Cys residue are highly conserved, as are other amino acids in the Yersinia and mammalian protein tyrosine phosphatases, suggesting that they use a common catalytic mechanism.
Protein tyrosine phosphatases.
The different subfamilies of PTPs and their conserved catalytic mechanism are described, and human diseases that result from disrupted PTP signaling are discussed, and the pursuit of P TPs as drug targets are discussed.