Abstract
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. The structure of the low-molecular-weight PTPase reveals an α/β protein containing a phosphate-binding loop motif at the amino end of helix αl. 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 PTP1B9. 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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Su, XD., Taddei, N., Stefani, M. et al. The crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase. Nature 370, 575–578 (1994). https://doi.org/10.1038/370575a0
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DOI: https://doi.org/10.1038/370575a0
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