Arginine kinase explained

arginine kinase
Ec Number:	2.7.3.3
Cas Number:	9026-70-4
Go Code:	0004054

In enzymology, arginine kinase is an enzyme that catalyzes the chemical reaction

ATP + L-arginine

\rightleftharpoons ADP + N^ω-phospho-L-arginine

Thus, the two substrates of this enzyme are ATP and L-arginine, whereas its two products are ADP and N^ω-phospho-L-arginine. Unlike the phosphoester bond, formed during the phosphorylation of serine, threonine or tyrosine residues, the phosphoramidate (P-N bond) in phospho-arginine is unstable at low pH (<8), making it difficult to detect with the traditional mass spectrometry protocols.^[1]

Arginine kinase belongs to the family of transferases, specifically those transferring phosphorus-containing groups (phosphotransferases) with a nitrogenous group as acceptor. This enzyme participates in arginine and proline metabolism.

Nomenclature

The systematic name of this enzyme class is

• ATP:L-arginine N^ω-phosphotransferase

Other names in common use include

• arginine phosphokinase,
• adenosine 5'-triphosphate: L-arginine phosphotransferase,
• adenosine 5'-triphosphate-arginine phosphotransferase,
• ATP:L-arginine N-phosphotransferasel ATP:L-arginine, and
• ω-N-phosphotransferase.

Function

In Gram-positive bacteria, such as Bacillus subtilis, the arginine kinase McsB phosphorylates the arginine residues on incorrectly folded or aggregated proteins to target them for degradation by the bacterial protease ClpC-ClpP (ClpCP).The phospho-arginine (pArg) modification is recognised by the N-terminal domain of ClpC, the protein-unfolding subunit of the ClpCP protease. Following recognition, the target protein is degraded by the ClpP subunit which has protease activity. Since phosphorylation reverses arginine's charge, the pArg modification has an unfolding effect on the target protein, easing its proteolytic degradation. Arginine phosphorylation is a dynamic post-translational modification, which can also be reversed by pArg-specific phosphatases, such as the bacterial YwlE. The pArg-ClpCP mechanism for protein degradation in bacteria is analogous to the eukaryotic ubiquitin-proteasome system.^[2]

Several studies have reported the presence of arginine kinases in eukaryotes.^{[3] [4]} A recent study identified arginine phosphorylation on 118 proteins in Jurkat cells, which were primarily proteins with DNA/RNA-binding activities.^[5] The function of arginine phosphorylation in eukaryotes however is still unknown.

Structural studies

As of late 2007, 8 structures have been solved for this class of enzymes, with PDB accession codes,,,,,,, and .

Further reading

• Elodi P, Szorenyi E . Properties of crystalline arginine-phosphoferase isolated from Crustacean muscle . Acta Physiologica Academiae Scientiarum Hungaricae . 9 . 4 . 367–379 . 1956 . 13339436 .
• Morrison JF, Griffiths DE, Ennor AH . The purification and properties of arginine phosphokinase . The Biochemical Journal . 65 . 1 . 143–153 . January 1957 . 13403885 . 1199841 . 10.1042/bj0650143 .
• Urbancsek J, Fancsovits P, Akos M, Tóthné Gilán Z, Hauzman E, Papp Z . [In vitro fertilization at our department. A decade's work in figures and facts (1994-2003)] . Orvosi Hetilap . 147 . 1 . 7–14 . January 2006 . 16519065 .
• Virden R, Watts DC, Baldwin E . Adenosine 5′-Triphosphate-Arginine Phosphotransferase from Lobster Muscle: Purification and Properties . The Biochemical Journal . 94 . 3 . 536–544 . March 1965 . 14340045 . 1206586 . 10.1042/bj0940536 .

Notes and References

1. Elsholz AK, Turgay K, Michalik S, Hessling B, Gronau K, Oertel D, Mäder U, Bernhardt J, Becher D, Hecker M, Gerth U . 6 . Global impact of protein arginine phosphorylation on the physiology of Bacillus subtilis . Proceedings of the National Academy of Sciences of the United States of America . 109 . 19 . 7451–7456 . May 2012 . 22517742 . 3358850 . 10.1073/pnas.1117483109 . 2012PNAS..109.7451E . free .
2. Trentini DB, Suskiewicz MJ, Heuck A, Kurzbauer R, Deszcz L, Mechtler K, Clausen T . Arginine phosphorylation marks proteins for degradation by a Clp protease . Nature . 539 . 7627 . 48–53 . November 2016 . 27749819 . 6640040 . 10.1038/nature20122 . 2016Natur.539...48T .
3. Levy-Favatier F, Delpech M, Kruh J . Characterization of an arginine-specific protein kinase tightly bound to rat liver DNA . European Journal of Biochemistry . 166 . 3 . 617–621 . August 1987 . 3609029 . 10.1111/j.1432-1033.1987.tb13558.x . free .
4. Wakim BT, Aswad GD . Ca(2+)-calmodulin-dependent phosphorylation of arginine in histone 3 by a nuclear kinase from mouse leukemia cells . The Journal of Biological Chemistry . 269 . 4 . 2722–2727 . January 1994 . 8300603 . 10.1016/s0021-9258(17)42003-5 . 25969282 . free .
5. Fu S, Fu C, Zhou Q, Lin R, Ouyang H, Wang M, Sun Y, Liu Y, Zhao Y . 6 . Widespread arginine phosphorylation in human cells - a novel protein PTM revealed by mass spectrometry . Science China Chemistry . March 2020 . 63 . 3 . 341–346 . 10.1007/s11426-019-9656-7 . 211217421 .