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Prediction of a ligand‐induced conformational change in the catalytic core of Cdc25A
Author(s) -
Kolmodin Karin,
Åqvist Johan
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01718-4
Subject(s) - conformational change , chemistry , protein tyrosine phosphatase , protein structure , dual specificity phosphatase , phosphatase , active site , cdc25 , ligand (biochemistry) , allosteric regulation , serine , stereochemistry , biophysics , biochemistry , phosphorylation , enzyme , receptor , biology , cell cycle , cyclin dependent kinase 1 , cell
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 of Cdc25A revealed that this enzyme has a completely different fold compared to all other phosphatases crystallised to date. The conformation of the active site residues does not seem very suitable for catalysis in this unliganded structure. We have studied some structural features of the Cdc25A apo ‐structure and a modelled Cdc25A‐ligand complex by molecular dynamics simulations. The simulations predict a conformational change in the peptide backbone 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 this type of conformational change is an important molecular switch in the catalytic process.