Phosphatases are enzymes that use water to cleave a phosphoric acid monoester into a phosphate ion and an alcohol molecule with a free hydroxyl group. Phosphatase enzymes work by catalyzing the hydrolysis of their substrate, and as such they are considered a subcategory of hydrolases.
Like all hydrolases, phosphatase enzymes are an essential catalyst in many biological functions, including cellular signaling and regulation via phosphorylation by protein kinases as well as dephosphorylation. Because they play such a key role in the of cells regulation, phosphatases are extremely valuable in the field of medical and pharmaceutical research. Phosphatase enzymes are not to be confused with phosphorylase enzymes. These catalyze the transfer of phosphate groups from hydrogen phosphate to an acceptor.
Phosphatases work by removing phosphate groups from molecules. Kinases, on the other hand work by catalyzing the transfer of phosphate groups to molecules from ATP synthase. Together, kinases and phosphatases combine to facilitate a form of post-translational modification that forms a key component of the regulatory network in every cell.
Phosphatases can dephosphorylate sites on their substrates which appear different in surprisingly specific ways, which brings us to...
Phosphatase Interactions and Functions
Studies reveal that so called "docking interactions" play a significant role in the binding of substrates. What makes phosphatase fascinating is their ability to recognize and interacts with various motifs of different substrates which bind with low affinity to docking sites on the phosphatase not contained within the active site. While each individual docking interaction is weak, when many interactions occur simultaneously this has a cumulative effect on the specificity of bindings.
Unlike kinases, phosphatase enzymes can recognize and catalyze broad range of substrates and reactions. In humans, for instance, Ser/Thr kinases outnumber Ser/Thr phosphatases ten to one. It’s worth noting that our incomplete knowledge of the human phosphatome (the complete set of phosphatases expressed in an organism, a tissue or its constituent cells) may at least partially account for this disparity.
It’s also important to note that many phosphatases have yet to be discovered, with a substrate yet to be identified for many of those that we do know. Nonetheless, well-studied phosphatase/kinase pairings consistently demonstrate that phosphatases exhibit greater variety in form and function than their kinase counterparts.
Protein phosphatases have even been observed to catalyze the dephosphorylation of nonprotein substrates. What’s more, dual-specificity tyrosine phosphatases can dephosphorylate serine residues as well as tyrosine residues, but also serine residues. As such, one single phosphatase can actually exhibit the properties of multiple phosphatase families.
The Enzyme Commission recognizes 104 distinct enzyme families within the larger class of phosphatases- although all still catalyze the same hydrolysis reaction. They are classified by the specificity of the substrate and the sequence homology of their catalytic domains.
In-vitro experiments have demonstrated that not only do phosphatase enzymes appear to recognize a wide range of different substrates, one substrate can be recognized by a range of different phosphatases. In-vivo experimentation, on the other hand, has shown phosphatase enzymes to be markedly more specific.