InterPro domain: IPR013024

Gamma-glutamyl cyclotransferase (GGCT) catalyzes the formation of pyroglutamic acid (5-oxoproline) from dipeptides containing gamma-glutamyl, and is a dimeric protein. In Homo sapiens, the protein is encoded by the gene C7orf24 [ 1 ]. The enzyme participates in the gamma-glutamyl cycle, which plays a pre-eminent role in glutathione homoeostasis [ 2 ]. The synthesis and metabolism of glutathione (L-gamma-glutamyl-L-cysteinylglycine) ties the gamma-glutamyl cycle to numerous cellular processes; glutathione acts as a ubiquitous reducing agent in reductive mechanisms involved in protein and DNA synthesis, transport processes, enzyme activity, and metabolism.

AIG2 (avrRpt2-induced gene) is an Arabidopsis protein that exhibits RPS2- and avrRpt2-dependent induction early after infection with Pseudomonas syringae pv maculicola strain ES4326 carrying avrRpt2 [ 3 , 4 ]. avrRpt2 is an avirulence gene that can convert virulent strains of P. syringae to avirulence on Arabidopsis thaliana, soybean, and bean. This GGCT-like domain is also found in bacterial tellurite-resistance proteins (TrgB) [ 5 ], butirosin biosynthesis protein BtrG [ 6 ], and in proteins described as ChaC, involved in a novel pathway for glutathione degradation [ 7 ].

1. The identification and structural characterization of C7orf24 as gamma-glutamyl cyclotransferase. An essential enzyme in the gamma-glutamyl cycle. J. Biol. Chem. 283, 22031-42
2. Glutathione. Annu. Rev. Biochem. 52, 711-60
3. Solution structure of Arabidopsis thaliana protein At5g39720.1, a member of the AIG2-like protein family. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 62, 490-3
4. Isolation of Arabidopsis genes that differentiate between resistance responses mediated by the RPS2 and RPM1 disease resistance genes. Plant Cell 8, 241-9
5. Bacterial tellurite resistance. Trends Microbiol. 7, 111-5
6. Biosynthesis of butirosin: transfer and deprotection of the unique amino acid side chain. Chem. Biol. 14, 379-86
7. Mammalian proapoptotic factor ChaC1 and its homologues function as γ-glutamyl cyclotransferases acting specifically on glutathione. EMBO Rep. 13, 1095-101