Little is known about the catalytic mechanism of serine/threonine specific protein phosphatases. Trans-phosphorylation reactions were unable to establish the presence of a phosphoryl-enyzme intermediate, [47]. Alkaline phosphatase catalyses dephosphorylation through a phosphoryl-serine enzyme intermediate, [48], whereas protein tyrosine phosphatases [49] proceed via a phosphoryl-cysteine intermediate. Low molecular mass phosphatases proceed via phosphoryl-cysteine [50] or phosphohistidine [51] intermediates. Recent evidence suggests that purple acid phosphatase may also function through a covalent phosphoryl-enzyme intermediate involving a histidine residue, [52]. However, the absence of invariant cysteines and serines in the protein serine/threonine phosphatases indicates that phosphoryl-cysteine and phosphoryl-serine intermediates do not occur in this family of phosphatases.
The less closely related reaction catalysed by phosphoglucomutase proceeds through a phosphoryl-histidine intermediate, and ATPases proceed via a phosphoryl-aspartate intermediate. Likely candidates for a putative intermediate in the protein serine/threonine phosphatases are therefore the invariant Asp 59 and 88 and His 61 and 139.