Phosphatase

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Overview

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 . 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.

Sub-types

Phosphatases can be subdivided based upon their substrate specificity.

Class	Example	Substrate	Reference
Tyrosine-specific phosphatases	PTP1B	Phospho-Tyrosine
Serine/Threonine specific phosphatases	PP2C	Phospho-Serine/Threonine
Dual Specificity Phosphatases	VHR	Phospho-Tyrosine/Serine/Threonine
Histidine Phosphatase	PHP	Phospho-Histidine
Lipid Phosphatase	PTEN	Phosphatidyl-Inositol-3,4,5-Triphosphate

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 ) or enable a protein-protein interaction to occur (e.g., SH3 domains ); 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

Serine/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 four known groups:

1. PP1 (α, β, γ1, γ2)
2. PP2A
3. PP2B (AKA calcineurin)
4. PP2C
5. PP4
6. PP5

The first three 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.

See also

• Acid salt
• Endonuclease/Exonuclease/phosphatase family

External links

• MeSH Phosphatases

Cost Effectiveness of Phosphatase

| group5 = Clinical Trials Involving Phosphatase | list5 = Ongoing Trials on Phosphatase at Clinical Trials.gov • Trial results on Phosphatase • Clinical Trials on Phosphatase at Google

| group6 = Guidelines / Policies / Government Resources (FDA/CDC) Regarding Phosphatase | list6 = US National Guidelines Clearinghouse on Phosphatase • NICE Guidance on Phosphatase • NHS PRODIGY Guidance • FDA on Phosphatase • CDC on Phosphatase

| group7 = Textbook Information on Phosphatase | list7 = Books and Textbook Information on Phosphatase

| group8 = Pharmacology Resources on Phosphatase | list8 = AND (Dose)}} Dosing of Phosphatase • AND (drug interactions)}} Drug interactions with Phosphatase • AND (side effects)}} Side effects of Phosphatase • AND (Allergy)}} Allergic reactions to Phosphatase • AND (overdose)}} Overdose information on Phosphatase • AND (carcinogenicity)}} Carcinogenicity information on Phosphatase • AND (pregnancy)}} Phosphatase in pregnancy • AND (pharmacokinetics)}} Pharmacokinetics of Phosphatase •

| group9 = Genetics, Pharmacogenomics, and Proteinomics of Phosphatase | list9 = AND (pharmacogenomics)}} Genetics of Phosphatase • AND (pharmacogenomics)}} Pharmacogenomics of Phosphatase • AND (proteomics)}} Proteomics of Phosphatase

| group10 = Newstories on Phosphatase | list10 = Phosphatase in the news • Be alerted to news on Phosphatase • News trends on Phosphatase</small>

| group11 = Commentary on Phosphatase | list11 = Blogs on Phosphatase

| group12 = Patient Resources on Phosphatase | list12 = Patient resources on Phosphatase • Discussion groups on Phosphatase • Patient Handouts on Phosphatase • Directions to Hospitals Treating Phosphatase • Risk calculators and risk factors for Phosphatase

| group13 = Healthcare Provider Resources on Phosphatase | list13 = Symptoms of Phosphatase • Causes & Risk Factors for Phosphatase • Diagnostic studies for Phosphatase • Treatment of Phosphatase

| group14 = Continuing Medical Education (CME) Programs on Phosphatase | list14 = CME Programs on Phosphatase

| group15 = International Resources on Phosphatase | list15 = Phosphatase en Espanol • Phosphatase en Francais

| group16 = Business Resources on Phosphatase | list16 = Phosphatase in the Marketplace • Patents on Phosphatase

| group17 = Informatics Resources on Phosphatase | list17 = List of terms related to Phosphatase

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