Phosphatase



A phosphatase is an 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 [1].   The free 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 phosphorus ion.

Sub-types

Phosphatases can be subdivided based upon their substrate specificity.

Class Example Substrate Reference
Tyrosine-specific phosphatases PTP1B Phospho-Tyrosine [2]
Threonine specific phosphatases PP2C Phospho-Serine/Threonine [3]
Dual Specificity Phosphatases VHR Phospho-Tyrosine/Serine/Threonine [4]
Histidine Phosphatase PHP Phospho-Histidine [5]
Lipid Phosphatase PTEN Phosphatidyl-Inositol-3,4,5-Triphosphate [6]

Physiological Relevance

Phosphatases act in opposition to hydrolysis, or is mediated by protein phosphatases.


Protein Phosphatases

Serine/threonine-specific protein phosphatases

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 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

References

  1. ^ Barford, D. Molecular mechanisms of the protein serine/threonine phosphatases, (1996) Trends Bioch Sci,21, 11, pp407
  2. ^ Zhong-Yin Zhang, PROTEIN TYROSINE PHOSPHATASES: Structure and Function, Substrate Specificity, and Inhibitor Development (2002), Annual Review of Pharmacology and Toxicology,42, pp209
  3. ^ Mumby, MC & Walter, G. Protein Serine/Threonine Phosphatases: Structure, Regulation, and Functions in Cell Growth (1993) Physiological Reviews,73,pp673
  4. ^ Camps, S et al, Dual specificity phosphatases: a gene family for control of MAP kinase function. (2000) FASEB J,1,pp16
  5. ^ Baumner, H et al, Expression of Protein Histidine Phosphatase in Escherichia coli, Purification, and Determination of Enzyme Activity. (2006), Methods Mol Biol, 365, pp247
  6. ^ Maehama, T. et al, The tumour suppressor PTEN: involvement of a tumour suppressor candidate protein in PTEN turnover (2004) Biochem. Soc. Trans. 32, pp343
  7. ^ Seger & Krebs,The MAPK Signalling cascade, FASEB J,9,pp726
  8. ^ Ladbury, JE, Measurement of the formation of complexes in tyrosine kinase-mediated signal transduction,(2007), Acta Cryst D,62,pp26
v • d • e
Pectinesterase - 6-phosphogluconolactonase - PAF acetylhydrolase

Diacylglycerol)

Phospholipase (A1, A2, B)
3.1.2: ThioesterasePalmitoyl thioesterase - Ubiquitin carboxy-terminal hydrolase L1
3.1.3: PhosphatasePurple acid phosphatases - Nucleotidase - Glucose 6-phosphatase - Fructose 1,6-bisphosphatase - Calcineurin - Phosphoprotein phosphatase (PP2A) - OCRL - Pyruvate dehydrogenase phosphatase - Fructose 2,6-bisphosphatase - Protein tyrosine phosphatase - Nuclease
 
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