| http://purl.uniprot.org/citations/21712391 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21712391 | http://www.w3.org/2000/01/rdf-schema#comment | "γ-Glutamyl transpeptidase (GGT) is a heterodimeric membrane enzyme that catalyzes the cleavage of extracellular glutathione and other γ-glutamyl-containing compounds. GGT is synthesized as a single polypeptide (propeptide) that undergoes autocatalytic cleavage, which results in the formation of the large and small subunits that compose the mature enzyme. GGT is extensively N-glycosylated, yet the functional consequences of this modification are unclear. We investigated the effect of N-glycosylation on the kinetic behavior, stability, and functional maturation of GGT. Using site-directed mutagenesis, we confirmed that all seven N-glycosylation sites on human GGT are modified by N-glycans. Comparative enzyme kinetic analyses revealed that single substitutions are functionally tolerated, although the N95Q mutation resulted in a marked decrease in the cleavage efficiency of the propeptide. However, each of the single site mutants exhibited decreased thermal stability relative to wild-type GGT. Combined mutagenesis of all N-glycosylation sites resulted in the accumulation of the inactive propeptide form of the enzyme. Use of N-glycosylation inhibitors demonstrated that binding of the core N-glycans, not their subsequent processing, is the critical glycosylation event governing the autocleavage of GGT. Although N-glycosylation is necessary for maturation of the propeptide, enzymatic deglycosylation of the mature wild-type GGT does not substantially impact either the kinetic behavior or thermal stability of the fully processed human enzyme. These findings are the first to establish that co-translational N-glycosylation of human GGT is required for the proper folding and subsequent cleavage of the nascent propeptide, although retention of these N-glycans is not necessary for maintaining either the function or structural stability of the mature enzyme."xsd:string |
| http://purl.uniprot.org/citations/21712391 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m111.248823"xsd:string |
| http://purl.uniprot.org/citations/21712391 | http://purl.uniprot.org/core/author | "Li C."xsd:string |
| http://purl.uniprot.org/citations/21712391 | http://purl.uniprot.org/core/author | "Hanigan M.H."xsd:string |
| http://purl.uniprot.org/citations/21712391 | http://purl.uniprot.org/core/author | "West M.B."xsd:string |
| http://purl.uniprot.org/citations/21712391 | http://purl.uniprot.org/core/author | "Wickham S."xsd:string |
| http://purl.uniprot.org/citations/21712391 | http://purl.uniprot.org/core/author | "Pavlovicz R.E."xsd:string |
| http://purl.uniprot.org/citations/21712391 | http://purl.uniprot.org/core/author | "Quinalty L.M."xsd:string |
| http://purl.uniprot.org/citations/21712391 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21712391 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/21712391 | http://purl.uniprot.org/core/pages | "28876-28888"xsd:string |
| http://purl.uniprot.org/citations/21712391 | http://purl.uniprot.org/core/title | "Autocatalytic cleavage of human gamma-glutamyl transpeptidase is highly dependent on N-glycosylation at asparagine 95."xsd:string |
| http://purl.uniprot.org/citations/21712391 | http://purl.uniprot.org/core/volume | "286"xsd:string |
| http://purl.uniprot.org/citations/21712391 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21712391 |
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