title: The crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase.
abstract: Protein tyrosine phosphorylation and dephosphorylation are central reactions for control of cellular division, differentiation and development. Here we describe the crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase (PTPase), a cytosolic phosphatase present in many mammalian cells. The enzyme catalyses the dephosphorylation of phosphotyrosine-containing substrates, and overexpression of the protein in normal and transformed cells inhibits cell proliferation. The structure of the low-molecular-weight PTPase reveals an alpha/beta protein containing a phosphate-binding loop motif at the amino end of helix alpha 1. This motif includes the essential active-site residues Cys 12 and Arg 18 and bears striking similarities to the active-site motif recently described in the structure of human PTP1B. 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. The structure also suggests a catalytic role for Asp 129 in the reaction cycle.
authors.affiliation: Department of Molecular Biology, University of Stockholm, Sweden.
authors.forename: X D
authors.initials: XD
authors.lastname: Su
authors.forename: N
authors.initials: N
authors.lastname: Taddei
authors.forename: M
authors.initials: M
authors.lastname: Stefani
authors.forename: G
authors.initials: G
authors.lastname: Ramponi
authors.forename: P
authors.initials: P
authors.lastname: Nordlund
mesh_terms: D000818:Animals; D001224:Aspartic Acid; D001665:Binding Sites; D002384:Catalysis; D002417:Cattle; D003461:Crystallography; D003545:Cysteine; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008970:Molecular Weight; D017433:Protein Structure, Secondary; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry*
chemical_list: D001224:Aspartic Acid; D017027:Protein Tyrosine Phosphatases; D003545:Cysteine