Section 13
Chapter 12,589

Structural basis for the catalytic activity of human serine/threonine protein phosphatase-5

Swingle, M.R.; Honkanen, R.E.; Ciszak, E.M.

Journal of Biological Chemistry 279(32): 33992-33999


ISSN/ISBN: 0021-9258
PMID: 15155720
DOI: 10.1074/jbc.m402855200
Accession: 012588224

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Serine/threonine protein phosphatase-5 (PP5) affects many signaling networks that regulate cell growth and cellular responses to stress. Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 A. From this structure we propose a mechanism for PP5-mediated hydrolysis of phosphoprotein substrates, which requires the precise positioning of two metal ions within a conserved Asp271-M1:M2-W1-His427-His304-Asp274 catalytic motif (where M1 and M2 are metals and W1 is a water molecule). The structure of PP5c provides a structural basis for explaining the exceptional catalytic proficiency of protein phosphatases, which are among the most powerful known catalysts. Resolution of the entire C terminus revealed a novel subdomain, and the structure of the PP5c should also aid development of type-specific inhibitors.

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