title: The structure and mechanism of protein phosphatases: insights into catalysis and regulation.
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.
authors.affiliation: Laboratory of Molecular Biophysics, University of Oxford, United Kingdom. davidb@biop.ox.ac.uk
authors.forename: D
authors.initials: D
authors.lastname: Barford
authors.forename: A K
authors.initials: AK
authors.lastname: Das
authors.forename: M P
authors.initials: MP
authors.lastname: Egloff
mesh_terms: D000818:Animals; D002384:Catalysis; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D005810:Multigene Family; D010749:Phosphoprotein Phosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D046911:Macromolecular Substances; D010749:Phosphoprotein Phosphatases; D017027:Protein Tyrosine Phosphatases