Phosphorylation and Dephosphorylation

Enzymes in the Phosphorylation and Dephosphorylation

Phosphorylation and Dephosphorylation process is controlled by the Enzymes. Enzymes play a great role in the Phosphorylation and Dephosphorylation process.

  • Phosphorylation reactions are catalyzed by a family of enzymes called protein kinases that use adenosine triphosphate (ATP) as a phosphate donor.
  • Phosphate groups are cleaved from phosphorylated enzymes by the action of phosphoprotein phosphatases
  • Amino acids with –OH groups are targets for phosphorylation.

Phosphorylation and Dephosphorylation

An important example of regulation by phosphorylation is seen in glycogen phosphorylase of muscle and liver which catalyzes the following reaction

Glycogen phosphorylase occurs in two forms:

  • Øthe more active phosphorylase a and
  • Øthe less active phosphorylase b.

The breakdown of glycogen is regulated by variations in the ratio of the two forms of glycogen phosphorylase a and b.

How can phosphorylation control enzyme activity?

−Phosphorylation refers to the addition of a phosphate to one of the amino acid side chains of a protein.

−Phosphates are negatively charged (with each phosphate group carrying two negative charges) so that their addition to a protein will change the characteristics of the protein.

−This change is often a conformational one, causing the protein to change how it is structured

 

Enzymatic conformational change upon phosphorylation:

Enzymatic conformational change upon phosphorylation is dramatically evident from the structures of the insulin receptor kinase (IRK) determined in the phosphorylated and unphosphorylated states as shown below.

Unphosphorylated IRK (left) and phosphorylated IRK (right)

The surface of IRK is shown in gray, except for the N-terminal domain in white in the left figure.  The activation loop in unphosphorylated IRK blocks binding of a substrate polypeptide chain, but moves out of the way, to the right, upon phosphorylation at three tyrosines.  Thus,  triple phosphorylation of this loop results in activation of kinase activity.

 

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