Part II. The Role of Phosphorylation
The chemical composition of the phosphoryl group confers upon the
phosphorylated protein certain
additional attributes which affects the structural, thermodynamic and
kinetic properties of the phosphorylated protein.
Some general principles which have become apparent from work
in the field are that:
- First, the phosphoryl group adds two negative charges to
the protein modifying and disrupting the initial electrostatic
interactions. This structural change can alter substrate binding
and catalytic activity of a phosphorylated enzyme.
- Second, the phosphoryl group can form three hydrogen bonds
or salt bridges with other protein residues.
This tetrahedral geometry makes the interactions highly directional.
- Third, phosphorylation can change the conformational equilibrium between
different functional states.
- Fourth, phosphorylation and
dephosphorylation reactions under the control of kinases and phosphatases,
can occur in less than a second or over a span of
hours which makes this system ideal as a regulatory process.
- Fifth, phosphorylation and dephosphorylation reactions can be
part of a cascade of reactions which can amplify a signal which has
an extracellular origin such as hormones and growth factors.
Original work on protein phosphorylation focussed on the
enzymes of the carbohydrate, lipid, and amino acid
metabolic pathways which were regulated by
Examination of the glucagon mediated signal transduction pathway of glycogen
breakdown serves to illustrate the above points.
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