InterPro domain: IPR000101

Gamma-glutamyltranspeptidase ( 2.3.2.2 ) (GGT) [ 1 ] catalyses the transfer of the gamma-glutamyl moiety of glutathione to an acceptor that may be an amino acid, a peptide or water (forming glutamate). GGT plays a key role in the gamma-glutamyl cycle, a pathway for the synthesis and degradation of glutathione and drug and xenobiotic detoxification [ 2 ]. In prokaryotes and eukaryotes, it is an enzyme that consists of two polypeptide chains, a heavy and a light subunit, processed from a single chain precursor by an autocatalytic cleavage. The active site of GGT is known to be located in the light subunit. The sequences of mammalian and bacterial GGT show a number of regions of high similarity [ 3 ]. Pseudomonas cephalosporin acylases ( 3.5.1 ) that convert 7-beta-(4-carboxybutanamido)-cephalosporanic acid (GL-7ACA) into 7-aminocephalosporanic acid (7ACA) and glutaric acid are evolutionary related to GGT and also show some GGT activity [ 4 ]. Like GGT, these GL-7ACA acylases, are also composed of two subunits. This entry also includes the highly similar Scoloptoxin SSD14 from Scolopendra dehaani. SSD14 (which is also cleaved into alpha and beta subunits) has been shown to induce human platelet aggregation [ 5 ].

As an autocatalytic peptidase GGT belongs to MEROPS peptidase family T3 (gamma-glutamyltransferase family, clan PB(T)). The active site residue for members of this family and family T1 is C-terminal to the autolytic cleavage site. The type example is gamma-glutamyltransferase 1 from Escherichia coli.

1. gamma-Glutamyl transpeptidase from kidney. Meth. Enzymol. 113, 400-19
2. Gamma-glutamyltransferase: nucleotide sequence of the human pancreatic cDNA. Evidence for a ubiquitous gamma-glutamyltransferase polypeptide in human tissues. Biochem. Pharmacol. 43, 2527-33
3. DNA sequence of the Escherichia coli K-12 gamma-glutamyltranspeptidase gene, ggt. J. Bacteriol. 171, 5169-72
4. Nucleotide sequence and expression in Escherichia coli of the cephalosporin acylase gene of a Pseudomonas strain. Biochim. Biophys. Acta 1132, 233-9
5. Venomic and transcriptomic analysis of centipede Scolopendra subspinipes dehaani. J. Proteome Res. 11, 6197-212