Wednesday, November 28, 2007

Regulating Enzyme Activity by Covalent Modification

 
Monday's Molecule #53 was phosphothreonine, one of several amino acid residues that can be phosphorylated.

UPDATE= The other major ones are serine and tyrosine but histidine, lysine, cysteine, aspartate and glutamate can also be phospohylated in some proteins as well as some modified amino acids like hydroxy-proline (Reinders, and Sickmann 2005).


Enzyme activity can be modified by covalent attachment of a phosphoryl group to an amino acid residue. In some cases the phosphorylated enzyme will be active while in other cases the phosphorylated enzyme will be inactive.

The classic examples of regulation by covalent modification are in the pathways for synthesis and degradation of glycogen [Regulating Glycogen Metabolism]. For example, the enzyme glycogen phosphorylase is responsible for breaking down glycogen and liberating glucose. Glycogen phosphorylase is active when phosphorylated and inactive when the phosphoryl group is removed. The phosphorylation is carried out by phosphorylase kinase and this enzyme is, itself, regulated by covalent modification. These enzymes are part of a larger signal transduction pathway involving several different phosphorylated enzymes.



Reinders, J. and Sickmann, A. (2005) State-of-the-art in phosphoproteomics. Proteomics 5:4052-4061.

7 comments :

  1. Wow...can't believe I missed this one, what with my Ph.D. in...protein phosphorylation!

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  2. For the sake of completeness, amino acids other than S,T,Y can be and apparently are reversibly phosphorylated, notably histidine.

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  3. Just to throw some extra trivia in there, even though phosphoserine is found in proteins and an aminoacyl-tRNA synthetasethat attaches the amino acid to tRNAs is found in nature, no known codon for phosphoserine exists. Biology is far more interesting than anything that is designed, IMHO.

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  4. Since we're listing phosphorylated amino acid side chains, let's not forget aspartate.

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  5. ponderingfool says,

    ... even though phosphoserine is found in proteins and an aminoacyl-tRNA synthetasethat attaches the amino acid to tRNAs is found in nature, no known codon for phosphoserine exists.

    The codons are UGU and UGC—the Cys codons. Those are the ones recognized by phosphoseryl-tRNA because the phosphoserine is converted to cysteine while it's still attached to tRNA but before it is incorporated into protein.

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  6. I have found what I think is a complete list of phosphorylated amino acids and incorporated that information into the post.

    Thanks to those who added examples.

    I checked with a colleague before posting and he couldn't think of any examples other than S, T, and Y. We agreed that my readers would soon point out the errors of our ways if we were wrong.

    Isn't blogging wonderful? It's a really good way to learn things.

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  7. The codons are UGU and UGC—the Cys codons. Those are the ones recognized by phosphoseryl-tRNA because the phosphoserine is converted to cysteine while it's still attached to tRNA but before it is incorporated into protein.
    ********************************

    The codons though are still for Cys not phosphoserine. Codons are defined by what amino acid they code for in translation not based on what amino acid gets attached to the corresponding tRNA.

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