PMID: 15152093

 

    Legend: Sugar

Title : Identification of the N-glycosylation sites on glutamate carboxypeptidase II necessary for proteolytic activity

Abstract :

1. Glutamate carboxypeptidase II ( GCPII ) is a membrane peptidase expressed in the prostate, central and peripheral nervous system, kidney, small intestine , and tumor-associated neovasculature
2. The GCPII form expressed in the central nervous system, termed NAALADase , is responsible for the cleavage of N-acetyl-L-aspartyl-L-glutamate (NAAG) yielding free glutamate in the synaptic cleft, and is implicated in various pathologic conditions associated with glutamate excitotoxicity
3. The prostate form of GCPII , termed prostate-specific membrane antigen ( PSMA ), is up-regulated in cancer and used as an effective prostate cancer marker
4. Little is known about the structure of this important pharmaceutical target
5. As a type II membrane protein , GCPII is heavily glycosylated
6. In this paper we show that N-glycosylation is vital for proper folding and subsequent secretion of human GCPII
7. Analysis of the predicted N-glycosylation sites also provides evidence that these sites are critical for GCPII carboxy peptidase activity
8. We confirm that all predicted N-glycosylation sites are occupied by an oligosaccharide moiety and show that glycosylation at sites distant from the putative catalytic domain is critical for the NAAG-hydrolyzing activity of GCPII calling the validity of previously described structural models of GCPII into question