Phosphatase


Phosphatase

A phosphatase is an enzyme that removes a phosphate group from its substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group (see dephosphorylation). This action is directly opposite to that of phosphorylases and kinases, which attach phosphate groups to their substrates by using energetic molecules like ATP. A common phosphatase in many organisms is alkaline phosphatase.

Phosphatases can be categorised into two main categories: Cysteine-dependent Phosphatases (CDPs) and metallo-phosphatases (which are dependent on metal ions in their active sites for activity).

Mechanism

CDPs catalyse the hydrolysis of a phosphoester bond via a phospho-cysteine intermediate [Barford, D. Molecular mechanisms of the protein serine/threonine phosphatases, (1996) "Trends Bioch Sci",21, 11, pp407] .The free cysteine nucleophile forms a bond with the phosphorus atom of the phosphate moiety, and the P-O bond linking the phosphate group to the tyrosine is protonated, either by a suitably positioned acidic amino acid residue (Asp in the diagram below) or a water molecule. The phospho-cysteine intermediate is then hydrolysed by another water molecule, thus regenerating the active site for another dephosphorylation reaction.

Metallo-phosphatases (eg PP2C) co-ordinate 2 catalytically essential metal ions within their active site. There is currently some confusion of the identity of these metal ions, as successive attempts to identify them yield different answers. There is currently evidence that these metals could be Magnesium, Manganese, Iron, Zinc, or any combination thereof. It is thought that a hydroxyl ion bridging the two metal ions takes part in nucleophilic attack on the phosphorus ion.

ub-types

Phosphatases can be subdivided based upon their substrate specificity.

Physiological relevance

Phosphatases act in opposition to kinases/phosphorylases, which add phosphate groups to proteins. The addition of a phosphate group may activate or de-activate an enzyme (e.g., Kinase signalling pathways [Seger & Krebs,The MAPK Signalling cascade, "FASEB J",9,pp726] ) or enable a protein-protein interaction to occur (e.g., SH3 domains [Ladbury, JE, Measurement of the formation of complexes in tyrosine kinase-mediated signal transduction,(2007), "Acta Cryst D",62,pp26] ); therefore phosphatases are integral to many signal transduction pathways. It should be noted that phosphate addition and removal do not necessarily correspond to enzyme activation or inhibition, and that several enzymes have separate phosphorylation sites for activating or inhibiting functional regulation. CDK, for example, can be either activated or deactivated depending on the specific amino acid residue being phosphorylated. Phosphates are important in signal transduction because they regulate the proteins to which they are attached. To reverse the regulatory effect, the phosphate is removed. This occurs on its own by hydrolysis, or is mediated by protein phosphatases.

Protein phosphatases

erine/threonine-specific protein phosphatases

Serine and threonine phosphates are stable under physiological conditions, so a phosphatase has to remove the phosphate to reverse the regulation. There are several known groups with numerous members in each:
# PP1 (α, β, γ1, γ2)
# PP2 (formerly 2A)
# PP3 (formerly 2b, also known as calcineurin)
# PP2C
# PP4
# PP5All but PP2C have sequence homology in the catalytic domain, but differ in substrate specifity.

Ser/Thr-specific protein phosphatases are regulated by their location within the cell and by specific inhibitor proteins.

ee also

*Acid salt
*Endonuclease/Exonuclease/phosphatase family

References

External links

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Look at other dictionaries:

  • phosphatase — [ fɔsfataz ] n. f. • av. 1949; de phosphate et ase ♦ Biochim. Enzyme qui catalyse la libération d acide phosphorique à partir de ses esters organiques. ● phosphatase nom féminin Enzyme libérant de l acide phosphorique, présente dans de nombreux… …   Encyclopédie Universelle

  • phosphatase — [fäs′fə tās΄] n. [< PHOSPHATE + ASE] any of various enzymes, found in body tissues and fluids, that hydrolyze phosphoric acid esters of organic compounds, liberating phosphate ions …   English World dictionary

  • phosphatase — Any of a group of enzymes (EC 3.1.3.x) that liberate orthophosphate from phosphoric esters. SEE ALSO: phosphohydrolases. acid p. a p. with an optimum pH of less than 7.0 (for several isozymes, it is 5.4), notably present in the prostate gland;… …   Medical dictionary

  • Phosphatase — Une phosphatase est une enzyme dont la fonction est d enlever un groupe phosphate d une molécule simple ou d une macromolécule biologique, par hydrolyse. En biotechnologie, elle peut agir sur l ADN et sur l ARN afin d empêcher leur… …   Wikipédia en Français

  • Phosphatase — Phosphatasen Enzymklassifikationen EC, Kategorie …   Deutsch Wikipedia

  • phosphatase — n. one of a group of enzymes capable of catalysing the hydrolysis of phosphoric acid esters. An example is glucose 6 phosphatase, which catalyses the hydrolysis of glucose 6 phosphate to glucose and phosphate. Phosphatases are important in the… …   The new mediacal dictionary

  • phosphatase — noun Date: 1912 an enzyme that accelerates the hydrolysis and synthesis of organic esters of phosphoric acid and the transfer of phosphate groups to other compounds: a. alkaline phosphatase b. acid phosphatase …   New Collegiate Dictionary

  • phosphatase — fosfatazė statusas T sritis chemija apibrėžtis Fermentas, katalizuojantis fosfatų atskėlimą. atitikmenys: angl. phosphatase rus. фосфатаза …   Chemijos terminų aiškinamasis žodynas

  • phosphatase — (fos fah teīs ) An enzyme that catalyzes the hydrolytic removal of phosphate from molecules …   Dictionary of microbiology

  • phosphatase — /fos feuh tays , tayz /, n. Biochem. any of several classes of esterases of varying specificity that catalyze the hydrolysis of phosphoric esters. [1910 15; PHOSPHATE + ASE] * * * …   Universalium


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