Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution

EMBO J. 1996 Dec 16;15(24):6798-809.


Protein phosphatase 2C (PP2C) is a Mn2+- or Mg2+-dependent protein Ser/Thr phosphatase that is essential for regulating cellular stress responses in eukaryotes. The crystal structure of human PP2C reveals a novel protein fold with a catalytic domain composed of a central beta-sandwich that binds two manganese ions, which is surrounded by alpha-helices. Mn2+-bound water molecules at the binuclear metal centre coordinate the phosphate group of the substrate and provide a nucleophile and general acid in the dephosphorylation reaction. Our model presents a framework for understanding not only the classical Mn2+/Mg2+-dependent protein phosphatases but also the sequence-related domains of mitochondrial pyruvate dehydrogenase phosphatase, the Bacillus subtilus phosphatase SpoIIE and a 300-residue domain within yeast adenyl cyclase. The protein architecture and deduced catalytic mechanism are strikingly similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence similarity, suggestive of convergent evolution of protein Ser/Thr phosphatases.

MeSH terms

  • Adenylyl Cyclases / chemistry
  • Amino Acid Sequence
  • Catalysis
  • Crystallography, X-Ray
  • Humans
  • Immunohistochemistry
  • Magnesium / metabolism
  • Manganese / metabolism
  • Molecular Sequence Data
  • Phosphoprotein Phosphatases / chemistry*
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Protein Conformation
  • Protein Phosphatase 2
  • Protein Phosphatase 2C
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • Substrate Specificity


  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Manganese
  • PPM1A protein, human
  • PPM1B protein, human
  • PPM1G protein, human
  • PTC1 protein, S cerevisiae
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2
  • Protein Phosphatase 2C
  • Adenylyl Cyclases
  • Magnesium