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In biochemistry, phosphorylation is understood to mean the reversible (reversible) attachment of a phosphoryl group to an organic molecule , in particular to proteins . The result is phosphoproteins . This phosphorylation represents (in addition to the allosteric and competitive inhibition ) the most important regulation of biological processes in the cell . Chemically, it is the formation of a phosphoric acid ester .

The principle of phosphorylation was first discovered during fermentation by Nobel Prize winner Arthur Harden and his student William John Young . Edmond Henri Fischer and Edwin G. Krebs received the 1992 Nobel Prize in Physiology and Medicine for clarifying the exact mechanism .

Phosphorylation of proteins

Enzymes involved in the process

The enzymes that catalyze the phosphorylation of proteins are called protein kinases . A phosphate group is covalently bound to an amino acid residue, usually with ATP as a substrate for the phosphate. Another category of enzymes, phosphatases , can reverse this process, i.e. H. the phosphate group is removed from the protein. Protein kinases and phosphatases are usually very specific and their activity can also be specifically controlled.


Since a phosphate group has a polar charge, phosphorylation often results in conformational changes in the protein, so that there are two possibly functionally different forms of the protein, depending on whether it is phosphorylated or not. Depending on the individual case, these two forms can represent activated or inactivated forms of a protein. Many transcription factors are activated in this way via signal transduction cascades , for example CREB .

Another form of influencing by phosphorylation is the regulation of protein binding sites. In particular, protein domains that mediate these interactions are phosphorylated and can no longer form protein complexes . Many receptors, such as G-protein coupled receptors , are regulated in their activity in this way. Protein phosphorylation and dephosphorylation thus have a regulatory function.

Location of phosphorylation

Mainly three amino acids are phosphorylated in proteins , namely those with a hydroxyl group in the side chain: tyrosine kinases bind the phosphate group to tyrosine , serine / threonine kinases to serine or threonine . Serine is the most frequently phosphorylated amino acid. The ratio of phosphorylation of Ser, Thr and Tyr is 1800: 200: 1.

The amino acids histidine, arginine, lysine, cysteine, glutamate and aspartate are phosphorylated even more rarely than tyrosine. However, there are also examples of these phosphorylations: In the phosphotransferase system (PTS), various histidines and a cysteine ​​are phosphorylated. In two-component systems used for signal transduction, conserved histidine or aspartate residues are phosphorylated.

Phosphorylation of other molecules

If other molecules (sugar, nucleotides ) are phosphorylated, this usually serves to provide chemical energy in the molecule in order to endothermic , i.e. H. to enable energy-consuming conversions. Polyphosphates such as ATP or creatine phosphate are used in the metabolism as a universal "energy currency" for intermediate storage and exchange of energy between different processes.

See also


Individual evidence

  1. Beyer-Walter, Textbook of Organic Chemistry, 22nd edition, S. Hirzel Verlag Stuttgart (1991) p. 891.