The crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase.
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.
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Department of Molecular Biology, University of Stockholm, Sweden.
Taddei
N
N
Stefani
M
M
Ramponi
G
G
Nordlund
P
P
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*
D001224:Aspartic Acid; D017027:Protein Tyrosine Phosphatases; D003545:Cysteine