This entry contains the human protein C7orf24 () which has been used as a cancer marker with a potential role in cell proliferation. It has been characterised as gamma-glutamyl cyclotransferase (GGCT), a homodimer of two 21kDa subunits, that catalyses the formation of 5-oxoproline (2-pyrrolidone-5-carboxylic acid, pyroglutamic acid) from gamma-glutamyl dipeptides () []. L-gamma-glutamyl-L-amino acid ->5-oxoproline + L-amino acidThe structure of GGCT has been solved. Its topology is unrelated to other enzymes associated with cyclotransferase-like activity and its structure has been termed the GGCT-fold, which appears to be related to the BtrG-like superfamily. A potential active site pocket contains a highly conserved glutamic acid (Glu(98)), which when converted to either Ala or Gln completely inactivates the enzyme without altering the overall fold [].This entry also includes GGCT gliK, GGCT aclK and GGCT verK from fungi. GGCT gliK is part of the gene cluster that mediates the biosynthesis of gliotoxin, a member of the epipolythiodioxopiperazine (ETP) class of toxins characterised by a disulfide bridged cyclic dipeptide [, ]. GGCT aclK mediates the biosynthesis of aspirochlorine []. GGCT verK mediates the biosynthesis of 11'-deoxyverticillin A, one of the dimeric epipolythiodioxopiperazines (ETPs) from the verticillin family that act as mycotoxins [].
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 []. The enzyme participates in the gamma-glutamyl cycle, which plays a pre-eminent role in glutathione homoeostasis []. 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.Structurally, GGCT is comprised of 7 beta strands and 2 alpha helices, and it folds into a five-stranded, antiparallel β-barrel [].
This entry represents a domain found in a group of gamma-glutamyl cyclotransferases (GGCTs), including AIG2 from Arabidopsis. GGCT is a ubiquitous enzyme found in bacteria, plants, and metazoans from Dictyostelium through to humans. It converts gamma-glutamylamines to free amines and 5-oxoproline [, , ].AIG2 is an Arabidopsis protein that exhibit RPS2- and avrRpt2-dependent induction early after infection with Pseudomonas syringae pv maculicola strain ES4326 carrying avrRpt2 []. Its structure consists of a five-stranded β-barrel surrounded by two α-helices and a small β-sheet. A long flexible α-helix protrudes from the structure at the C-terminal end. Conserved residues in a hydrophilic cavity, which are able to bind small ligands, may act as an active site in AIG2-like proteins [].
