Identification of a human gamma-glutamyl cleaving enzyme related to, but distinct from, gamma-glutamyl transpeptidase.
We have cloned a 2.4-kilobase cDNA from a human placental cDNA library by using a gamma-glutamyl transpeptidase [GGT; gamma-glutamyltransferase, (5-glutamyl)-peptide:amino acid 5-glutamyltransferase, EC 2.3.2.2] probe. The deduced amino acid sequence of this cDNA, GGT-rel, exhibited an overall similarity of 39.5% with human GGT. Sequences that could represent a heavy and a light chain, analogous to GGT, as well as a putative transmembrane region were identified in GGT-rel. Transfectants overexpressing GGT-rel were tested for their ability to catalyze cleavage of the gamma-glutamyl moiety from natural and synthetic substrates for GGT. Experiments with glutathione added to the medium suggested that GGT-rel could hydrolyze the gamma-glutamyl moiety. More definitive evidence was obtained in experiments in which this protein converted leukotriene C4 to leukotriene D4. However, GGT-rel did not convert synthetic substrates that are commonly used to assay GGT. Our results indicate that GGT can no longer be considered the only enzyme capable of cleaving the gamma-glutamyl linkage of leukotriene C4 and, most likely, of other natural compounds.
Department of Pathology, Childrens Hospital of Los Angeles, CA 90027.
N
N
Heisterkamp
E
E
Rajpert-De Meyts
L
L
Uribe
H J
HJ
Forman
J
J
Groffen
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002460:Cell Line; D003001:Cloning, Molecular; D005260:Female; D015723:Gene Library; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D015183:Restriction Mapping; D013189:SRS-A / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection; D005723:gamma-Glutamyltransferase / Q000235:genetics* / Q000378:metabolism
D013189:SRS-A; C069812:gamma-glutamyltransferase related enzyme; D005723:gamma-Glutamyltransferase