The structure and mechanism of protein phosphatases: insights into catalysis and regulation

Annual Review of Biophysics and Biomolecular Structure
D BarfordM P Egloff

Abstract

Eukaryotic protein phosphatases are structurally and functionally diverse enzymes that are represented by three distinct gene families. Two of these, the PPP and PPM families, dephosphorylate phosphoserine and phosphothreonine residues, whereas the protein tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosine amino acids. A subfamily of the PTPs, the dual-specificity phosphatases, dephosphorylate all three phosphoamino acids. Within each family, the catalytic domains are highly conserved, with functional diversity endowed by regulatory domains and subunits. The protein Ser/Thr phosphatases are metalloenzymes and dephosphorylate their substrates in a single reaction step using a metal-activated nucleophilic water molecule. In contrast, the PTPs catalyze dephosphorylation by use of a cysteinyl-phosphate enzyme intermediate. The crystal structures of a number of protein phosphatases have been determined, enabling us to understand their catalytic mechanisms and the basis for substrate recognition and to begin to provide insights into molecular mechanisms of protein phosphatase regulation.

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Methods Mentioned

BETA
two hybrid
biosensor
GTPases

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