Phosphatases

Abstract

Phosphatases are enzymes that catalyze the hydrolysis of a phosphate monoester, or, in other words, the phosphoryl transfer from an ester substrate to water. Some phosphatases, utilizing a binuclear metal center, accomplish this reaction in a single step. Others, some of which also utilize two‐metal ion catalysis and some of which do not, first form a phosphoenzyme intermediate, which is hydrolyzed by attack of water in a second step. Protein‐tyrosine phosphatases utilize a conserved cysteine residue and form a phosphocysteine intermediate. Alkaline phosphatases utilize two zinc ions and form a phosphoserine intermediate. The protein serine/threonine phosphatases and the purple acid phosphatases have a dinuclear metal center and catalyze the direct transfer of the phosphoryl group to a metal‐coordinated hydroxide. A number of phosphatases have been found capable of catalyzing other hydrolysis reactions, such as those of sulfate esters, or of phosphate and phosphonate diesters. Such so‐called promiscuous activities arise from the ability of the enzymes to stabilize a trigonal bipyramidal transition state, which is common to the reaction of its native substrate as well as the alternate substrates.

Insights into the Phosphoryl Transfer Mechanism of Cyclin-Dependent Protein Kinases from ab Initio QM/MM Free-Energy Studies

“…The chemical step catalyzed by CDK2 is the transfer of a phosphoryl group from the γ position of ATP to the hydroxyl group of a Ser or Thr residue of the substrate. For such phosphoryl transfer reactions, three limiting-case mechanisms are possible. , The dissociative (D N + A N ) mechanism envisions an initial dissociation of a free metaphosphate followed by addition. The associative (A N + D N ) mechanism, on the other hand, features a pentacovalent phosphorane intermediate, flanked by two transition states.…”