The Role of Glycosylation in the Autocleavage of Human γGlutamyl Transpeptidase 1

Abstract

N-glycosylation is a widely occurring post-translational modification in which an oligosaccharide is linked to the amide nitrogen of an Asn side chain in the sequence Asn-XThr/Ser (where X≠Pro). This modification has been shown to play a role in protein folding, trafficking, stability, and function. Here we use molecular dynamics simulations of glycosylated and unglycosylated structures to address the role of N-glycosylation in the regulation of enzymatic function in human γ-Glutamyltranspeptidase 1 (hGGT1; EC 2.3.2.2). hGGT1 is a conserved enzyme known to play a role in maintaining cysteine levels in the body and in regulating intra-cellular redox status. The crystal structure of hGGT1 indicates that it is post-translationally modified by N-glycosylation at seven sites, and glycosylation at N95 has been shown to be the most critical to the ability of the enzyme to undergo activation through autocatalysis.