Phosphatases

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Phosphatases
Enzyme Classifications
EC, category 3.1.3.- ,  hydrolase
Response type Hydrolysis of a phosphoric acid ester bond
Substrate Phosphoric acid monoester + H 2 O
Products Alcohol + phosphate
EC, category 3.1.4.- ,  hydrolase
Response type Hydrolysis of orthophosphoric acid ester bonds
Substrate Orthophosphoric acid ester + H 2 O
Products Alcohol + phosphoric acid ester
EC, category 3.1.5.- ,  hydrolase
Response type Hydrolysis of triphosphoric acid ester bonds
Substrate Triphosphoric acid ester + H 2 O
Products Alcohol + PPP i

Phosphatases are a group of enzymes that split off phosphoric acid from phosphoric acid esters or polyphosphates through the addition of water ( hydrolysis ) . They perform the reverse reaction of a kinase . The best-known representatives of this group are the enzymes acid phosphatase and alkaline phosphatase, named after their pH optimum . Most common are the nucleic acid cleaving nucleases that depolymerize DNA or RNA , i.e. H. disassemble into fragments. They belong to the enzyme class EC 3.1.-.- .  

Protein phosphatases

Protein phosphatases remove the phosphate residues attached to amino acid residues (mostly serine and threonine or tyrosine ) by protein kinases . Both phosphorylation and dephosphorylation are important components of signal transmission , e.g. B. in metabolism , where the enzymes concerned are thereby modulated in their activity. All enzymes involved in the breakdown of glycogen ( phosphorylase kinase , glycogen phosphorylase ) are active in the phosphorylated state, whereas the synthesis enzyme ( UDP-glycogen synthase ) is inactive. Phosphatases reverse these relationships.

In 2013 there were almost 20,000 registered phosphoproteins with more than 206,000 phosphorylation sites. About 86 percent of mammalian phosphoproteins are modified in serines, about twelve percent in threonines and about two percent in tyrosines. A little under four percent of human proteins are protein phosphatases. There are four classes of protein phosphatases, alkaline phosphatases , Ser / Thr-specific, Tyr-specific, or dual-specific protein phosphatases.

Alkaline phosphatases come from a. in the intestine and not only dephosphorylate proteins, some isoenzymes are inhibited by homoarginine or levamisole and its derivatives, others by imidazole .

The Ser / Thr-specific protein phosphatases are further subdivided into type I or type II. Type I phosphatases such as B. PP1 are inhibited by the heat-stable proteins inhibitor-1 and inhibitor-2 and preferentially dephosphorylate the β-subunit of phosphorylase kinase . Type II phosphatases are divided into spontaneous activation (subtype A), Ca 2+ -dependent or Mg 2+ -dependent activation and preferentially dephosphorylate the α-subunit of phosphorylase kinase. Ser / Thr-specific phosphatases are u. a. inhibited by okadaic acid , calyculin A , cyclosporine , FK-506 , microcystin-LR , tautomycin , fostriecin and cantharidin , with varying effectiveness against the different isoforms.

The Tyr-specific protein phosphatases have a conserved common catalytic protein domain. You will u. a. inhibited by orthovanadate , peroxovanadate and sodium fluoride .

The dual-specific phosphatases are divided into three groups, with DSP1, DSP2, DSP4 and DSP5 in group I, furthermore DSP6, DSP7, DSP9 and DSP10 in group II and DSP8 and DSP16 in group III, with group III having PEST sequences . DSP1, DSP2, DSP4 and DSP5 localize in the nucleus , DSP6, DSP7 and DSP16 in the cytosol , DSP8, DSP9 and DSP10 in both compartments and DSP18 and DSP21 in mitochondria . Dual specific protein phosphatases are u. a. inhibited by orthovanadates.

Serine / threonine-specific protein phosphatases

There are four classes that are regulated by their localization in the cell and by specific inhibitors:

The first three enzymes show considerable homology in the catalytic domain despite different substrate specificities .

literature

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