The cell cycle control phosphatases Cdc25 are dual specificity phosphatases
that dephosphorylate both phosphothreonine and phosphotyrosine residues on
their substrate proteins. The determination of the apo-protein structure o
f Cdc25A revealed that this enzyme has a completely different fold compared
to all other phosphatases crystallised to date. The conformation of the ac
tive site residues does not seem very suitable for catalysis in this unliga
nded structure. We hare studied some structural features of the Cdc25A apo-
structure and a modelled Cdc25A-ligand complex by molecular dynamics simula
tions. The simulations predict a conformational change in the peptide backb
one of the complex, which is not observed in the apo-structure. This ligand
-induced conformational change yields a structure that is similar to other
protein tyrosine phosphatase-ligand complexes that have been crystallised.
The change in conformation takes place in the position between a serine and
a glutamic acid residue in the phosphate binding loop. We suggest that thi
s type of conformational change is an important molecular switch in the cat
alytic process. (C) 2000 Federation of European Biochemical Societies.