In biochemistry, a phosphatase is an enzyme that uses water to cleave a phosphoric acid Ester into a phosphate ion and an alcohol. Because a phosphatase enzyme catalysis the hydrolysis of its substrate, it is a subcategory of .
Phosphatase enzymes are not to be confused with phosphorylase enzymes, which catalyze the transfer of a phosphate group from hydrogen phosphate to an acceptor. Due to their prevalence in cellular regulation, phosphatases are an area of interest for pharmaceutical research.
Biochemistry
Phosphatases
catalysis the
hydrolysis of a phosphomonoester, removing a
phosphate moiety from the substrate. Water is split in the reaction, with the -OH group attaching to the phosphate ion, and the H+ protonating the
hydroxyl group of the other product. The net result of the reaction is the destruction of a phosphomonoester and the creation of both a phosphate ion and a molecule with a free hydroxyl group.
Phosphatases are able to dephosphorylate seemingly different sites on their substrates with great specificity. Identifying the "phosphatase code," that is, the mechanisms and rules that govern substrate recognition for phosphatases, is still a work in progress, but the first comparative analysis of all the protein phosphatases encoded across nine eukaryotic 'phosphatome' is now available.
Functions
In contrast to kinases, phosphatase enzymes recognize and catalyze a wider array of substrates and reactions. For example, in humans, Ser/Thr kinases outnumber Ser/Thr phosphatases by a factor of ten.
To some extent, this disparity results from incomplete knowledge of the human
phosphatome, that is, the complete set of phosphatases expressed in a cell, tissue, or organism.
Many phosphatases have yet to be discovered, and for numerous known phosphatases, a substrate has yet to be identified. However, among well-studied phosphatase/kinase pairs, phosphatases exhibit greater variety than their kinase counterparts in both form and function; this may result from the lesser degree of conservation among phosphatases.
Distinctions
Phosphatases should not be confused with
phosphorylases, which add phosphate groups.
|
Transferase
(EC 2.4, 2.7.7) | | transfer group = A
= glycosyl/nucleotidyl group |
Hydrolase
(EC 3) | | |
Transferase
| | transfer group = P |
P = phosphonate group, OP = phosphate group,
or = inorganic phosphate |
Protein phosphatases
A protein phosphatase is an enzyme that dephosphorylates an amino acid residue of its protein substrate. Whereas protein kinases act as signaling molecules by phosphorylating proteins, phosphatases remove the phosphate group, which is essential if the system of intracellular signaling is to be able to reset for future use. The tandem work of kinases and phosphatases constitute a significant element of the cell's regulatory network.
Phosphorylation (and dephosphorylation) is among the most common modes of posttranslational modification in proteins, and it is estimated that, at any given time, up to 30% of all proteins are phosphorylated.
Two notable protein phosphatases are PP2A and PP2B. PP2A is involved in multiple regulatory processes, such as DNA replication, metabolism, transcription, and development. PP2B, also called calcineurin, is involved in the proliferation of ; because of this, it is the target of some drugs that seek to suppress the immune system.
Nucleotidases
A
nucleotidase is an enzyme that catalyzes the hydrolysis of a
nucleotide, forming a
nucleoside and a phosphate ion.
Nucleotidases are essential for cellular
homeostasis, because they are partially responsible for maintaining a balanced ratio of nucleotides to nucleosides.
Some nucleotidases function outside the cell, creating nucleosides that can be transported into the cell and used to regenerate nucleotides via salvage pathways.
Inside the cell, nucleotidases may help to maintain energy levels under stress conditions. A cell deprived of oxygen and nutrients may
catabolize more nucleotides to boost levels of nucleoside triphosphates such as ATP, the primary energy currency of the cell.
In gluconeogenesis
Phosphatases can also act on
, such as intermediates in
gluconeogenesis. Gluconeogenesis is a
Biosynthesis pathway wherein
glucose is created from noncarbohydrate precursors; the pathway is essential because many tissues can only derive energy from glucose.
Two phosphatases, glucose-6-phosphatase and fructose-1,6-bisphosphatase, catalyze irreversible steps in gluconeogenesis.
Each cleaves a phosphate group from a six-carbon
Sugar phosphates intermediate.
Classification
Within the larger class of phosphatase, the Enzyme Commission recognizes 104 distinct enzyme families. Phosphatases are classified by substrate specificity and sequence homology in catalytic domains.
Despite their classification into over one hundred families, all phosphatases still catalyze the same general hydrolysis reaction.
In in-vitro experiments, phosphatase enzymes seem to recognize many different substrates, and one substrate may be recognized by many different phosphatases. However, when experiments have been carried out in-vivo, phosphatase enzymes have been shown to be incredibly specific.
See also
-
Acid phosphatase
-
Alkaline phosphatase
-
Endonuclease/Exonuclease/phosphatase family
-
Kinase
-
Phosphatome
-
Phosphotransferase
-
Protein phosphatase
-
Protein phosphatase 2 (PP2A)
External links
