The crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase

  title={The crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase},
  author={Xiao-Dong Su and Niccol{\`o} Taddei and Massimo Stefani and Giampietro Ramponi and P{\"a}r Nordlund},
PROTEIN tyrosine phosphorylation and dephosphorylation are central reactions for control of cellular division, differentiation and development1. Here we describe the crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase (PTPase)2, a cytosolic phosphatase present in many mammalian cells. The enzyme catalyses the dephosphorylation of phosphotyrosine-containing substrates3–6, and overexpression of the protein in normal and transformed cells inhibits cell proliferation7,8… 
Crystal Structure of a Human Low Molecular Weight Phosphotyrosyl Phosphatase
The x-ray crystallographic structure of a human low molecular weight PTPase solved by molecular replacement to 2.2 Å is presented and possible aromatic residue interactions with the phosphotyrosine substrate are proposed from an examination of the binding site of the inhibitors.
Solution Structure of a Low-Molecular-Weight Protein Tyrosine Phosphatase from Bacillus subtilis
  • Huimin Xu, B. Xia, C. Jin
  • Chemistry
    Journal of bacteriology
  • 2006
The solution structure of YwlE, an LMW PTP identified from the gram-positive bacteria Bacillus subtilis, is reported and the solution structure in combination with the backbone dynamics provides insights into the mechanism of substrate specificity of bacterial L MW PTPs.
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.
The Inactivation Mechanism of Low Molecular Weight Phosphotyrosine-protein Phosphatase by H2O2 *
It is suggested that oxidative stress conditions and other processes producing hydrogen peroxide regulate the LMW-PTP in thecell, because a physiological concentration of H2O2 produces enzyme inactivation and considering that the activity is restored by reduction with low molecular weight thiols.
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.
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 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 role of Cys12, Cys17 and Arg18 in the catalytic mechanism of low-M(r) cytosolic phosphotyrosine protein phosphatase.
Phosphoenzyme-trapping experiments enable us to identify Cys12 as the active-site residue that performs the nucleophilic attack at the phosphorus atom of the substrate to produce a phosphoenzyme covalent intermediate.
Leaving group dependence and proton inventory studies of the phosphorylation of a cytoplasmic phosphotyrosyl protein phosphatase from bovine heart.
The D2O solvent isotope effect and proton inventory experiments indicate that only one proton is "in flight" in the transition state of the phosphorylation process and that this proton transfer is responsible for the reduction of effective charge on the leaving oxygen.
The complete amino acid sequence of the low molecular weight cytosolic acid phosphatase.
The complete amino acid sequence of the low molecular weight acid phosphatase from bovine liver is presented, which is located in the cytosol, is not inhibited by L-(+)-tartrate and fluoride ions, but is inhibited by sulfhydryl reagents.
Cloning, expression, and catalytic mechanism of the low molecular weight phosphotyrosyl protein phosphatase from bovine heart.
The first representative of a group of mammalian, low molecular weight phosphotyrosyl protein phosphatases was cloned, sequenced and expressed in Escherichia coli. Using a 61-mer oligonucleotide
Overexpression of a synthetic phosphotyrosine protein phosphatase gene inhibits normal and transformed cell growth
The results indicate that overexpression of PTPase might interfere with mitogenic signalling pathways in both normal and transformed cells, and propose a role for PTP enzyme in the control of cell proliferation.