InterPro domain: IPR014746

The C-terminal catalytic domains of glutamine synthetase and the guanido kinase family (which includes creatine kinase and arginine kinase) share a common structural fold, namely a common core consisting of two beta-alpha-beta2-alpha repeats [ 1 ].

Glutamine synthetase ( 6.3.1.2 ) (GS) [ 2 ] plays an essential role in the metabolism of nitrogen by catalysing the condensation of glutamate and ammonia to form glutamine. There seem to be three different classes of GS [ 3 , 4 , 5 ]. Class I enzymes (GSI) are specific to prokaryotes, and are oligomers of 12 identical subunits; the activity of GSI-type enzyme is controlled by the adenylation of a tyrosine residue. Class II enzymes (GSII) are found in eukaryotes and in bacteria, and are oligomers of 8 identical subunits. Class III enzymes (GSIII) have been found in Bacteroides fragilis in Butyrivibrio fibrisolvens, and are oligomers of six identical subunits. While the three classes of GS's are clearly structurally related, the sequence similarities are not so extensive.

ATP:guanido phosphotransferases are a family of structurally and functionally related enzymes [ 6 , 7 ] that reversibly catalyse the transfer of phosphate between ATP and various phosphogens. The enzymes belonging to this family include:

• Glycocyamine kinase ( 2.7.3.1 ), which catalyses the transfer of phosphate from ATP to guanidoacetate.
• Arginine kinase ( 2.7.3.3 ), which catalyses the transfer of phosphate from ATP to arginine.
• Taurocyamine kinase ( 2.7.3.4 ), an annelid-specific enzyme that catalyses the transfer of phosphate from ATP to taurocyamine.
• Lombricine kinase ( 2.7.3.5 ), an annelid-specific enzyme that catalyses the transfer of phosphate from ATP to lombricine.
• Smc74, a cercaria-specific enzyme from Schistosoma mansoni [ 8 ].
• Creatine kinase ( 2.7.3.2 ) (CK) [ 8 , 9 ], which plays an important role in energy metabolism of vertebrates.

1. Mitochondrial creatine kinase--a square protein. Curr. Opin. Struct. Biol. 7, 811-8
2. Advances in the enzymology of glutamine synthesis. Adv. Enzymol. Relat. Areas Mol. Biol. 72, 9-42
3. Evolution of the glutamine synthetase gene, one of the oldest existing and functioning genes. Proc. Natl. Acad. Sci. U.S.A. 90, 3009-13
4. Glutamine synthetase II in Rhizobium: reexamination of the proposed horizontal transfer of DNA from eukaryotes to prokaryotes. J. Mol. Evol. 29, 422-8
5. Evolutionary relationships of bacterial and archaeal glutamine synthetase genes. J. Mol. Evol. 38, 566-76
6. A cloned ATP:guanidino kinase in the trematode Schistosoma mansoni has a novel duplicated structure. J. Biol. Chem. 265, 6582-8
7. Isolation and sequence analysis of the gene for arginine kinase from the chelicerate arthropod, Limulus polyphemus: insights into catalytically important residues. Biochim. Biophys. Acta 1246, 197-200
8. The creatine-creatine phosphate energy shuttle. Annu. Rev. Biochem. 54, 831-62
9. Separate nuclear genes encode sarcomere-specific and ubiquitous human mitochondrial creatine kinase isoenzymes. J. Biol. Chem. 265, 6921-7