Mechanism of Cdc25B phosphatase with the small molecule substrate p-nitrophenyl phosphate from QM/MM-MFEP calculations.

ABSTRACT: Cdc25B is a dual-specificity phosphatase that catalyzes the dephosphorylation of the Cdk2/CycA protein complex. This enzyme is an important regulator of the human cell cycle and has been identified as a potential anticancer target. In general, protein tyrosine phosphatases are thought to bind the dianionic form of the phosphate and employ general acid catalysis via the Asp residue in the highly conserved WPD-loop. However, the Cdc25 phosphatases form a special subfamily based on their distinct differences from other protein tyrosine phosphatases. Although Cdc25B contains the (H/V)CX(5)R catalytic motif present in all other protein tyrosine phosphatases, it lacks an analogous catalytic acid residue. No crystallographic data currently exist for the complex of Cdc25B with Cdk2/CycA, so in add

SUBMITTER: Parks JM 

PROVIDER: S-EPMC2712249 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature