SerineAre you looking for a residue to modify? Well, you have to try serine. This amino acid is a champ when it comes to modifications. First, it is clearly hydrophilic, therefore, it can be exposed to the solvent, and then an enzyme can easily access it and place an attachment on the hydroxyl-group: phosphate, sugar moiety, acetyl, etc. Protein kinanses most commonly phosphorylate serine residues, while phosphatases dephosphorylate them, and both processes are often running at the same time. If you think, this is a waste of precious ATP, you’ll be wrong. Phosporylation-dephosporylation of serine and threonine is one of the regulatory mechanisms in eukaryotic cells, thus making them able to react to changing conditions by reducing the activity of enzymes, rather than switching them off completely. For example, pyruvate dehydrogenase complex can have a few phosphorylation sites, which would reduce the activity of the enzyme, when there is enough ATP, and no pyruvate shall be burned in the TCA cycle. Phosposylation-dephosphorylation is also involved in genetic regulation, and malfunction of this process can promote cancer.
Role in catalysis. Well, this is very important function of this amino acid. Many catalytic triades employ serine as a nucleophilic end of a catalytic cascade. Likewise, acetyl-choline esterase, one of the most efficient enzymes, it is responsible for rapid degradation of acetylcholine neurotransmitter in sinapses, after neuronic signal has been transmitted. The nucleophile here is a serine side chain. Blocking of this serine is targeted by chemical weapons as well as agrochemical insecticides. Would you like to try some Russian tea from Salisbury? The reason, why sarin, soman and other frequently used organophosphates are such efficient weapons, is due to their covalent binding to the catalytic serine in acetylcholinesterase. Although, this is only one example, many enzymes cannot function without catalytic serine, and its function can rarely be overtaken by threonine, since threonine has a lower degree of side-chain rotational freedom.
Participation in translation and protein build-up is not a main function of serine in cells, while its major role is C1-metabolism. Conversion of serine to glycine releases a methylene-tetrahydropholate, which is a source of C1-unit in many cellular processes, such as production of thymidine or methionine. Tryptophan is synthesizes by condensing serine with an indole. Biosynthesis of cysteine also requires serine. Selenocysteine is a special canonical amino acid, which is made pre-translationaly from serine: because free selenocusteine would quickly degrade in the cytosol, first, a tRNA-loaded serine side chain is converted by a special enzyme into selenocysteine residue, and then this is brought on the ribosome, where the amino acid is incorporated into proteins.
Overall, serine is highly abundant and versatile amino acid. But beware of its evil twin brother, D-serine, which may inhibit cellular growth, or damage kidneys.
- Krug, A. W. et al. Why is D-serine nephrotoxic and a-aminoisobutyric acid protective? Am. J. Physiol. Renal Physiol., 293, 2007, F382-F390, doi: 10.1152/ajprenal.00441.2006
The title speaks it all. The study addresses toxicity of serine, and has an interesting introduction.
- Ekici, O. D. et al. Unconventional serine proteases: Variations on the catalytic Ser/His/Asp triad configuration. Protein Sci., 17, 2008, 2023-2037, doi: 10.1110/ps.035436.108
The review illustrates differences in catalytic triads of serine proteases.
- Endicott et al. The structural basis for control of eukaryotic protein kinases. Annu. Rev. Biochem., 81, 2012, 587-613, doi: 10.1146/annurev-biochem-052410-090317
The review provides an overview of protein kinases, their structures, activation and general aspects.
- Lizcano, A. et al. A role for glycosylated serine-rich repeat proteins in Gram-positive bacterial pathogenesis. Mol. Oral. Microbiol., 27, 2012, 257-269, doi: 10.1111/j.2041-1014.2012.00653.x
The review discusses involvement of serine-rich repeats in bacterial pathogenicity.
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