Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A

Cell. 1998 May 15;93(4):617-25. doi: 10.1016/s0092-8674(00)81190-3.


Cdc25 phosphatases activate the cell division kinases throughout the cell cycle. The 2.3 A structure of the human Cdc25A catalytic domain reveals a small alpha/beta domain with a fold unlike previously described phosphatase structures but identical to rhodanese, a sulfur-transfer protein. Only the active-site loop, containing the Cys-(X)5-Arg motif, shows similarity to the tyrosine phosphatases. In some crystals, the catalytic Cys-430 forms a disulfide bond with the invariant Cys-384, suggesting that Cdc25 may be self-inhibited during oxidative stress. Asp-383, previously proposed to be the general acid, instead serves a structural role, forming a conserved buried salt-bridge. We propose that Glu-431 may act as a general acid. Structure-based alignments suggest that the noncatalytic domain of the MAP kinase phosphatases will share this topology, as will ACR2, a eukaryotic arsenical resistance protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Disulfides / chemistry
  • Humans
  • Models, Molecular*
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Tyrosine Phosphatases / chemistry*
  • Sequence Alignment
  • Substrate Specificity
  • cdc25 Phosphatases*


  • Disulfides
  • CDC25A protein, human
  • Protein Tyrosine Phosphatases
  • cdc25 Phosphatases

Associated data

  • PDB/1C25