title: Proteolytic Cleavage Driven by Glycosylation.
abstract: Proteolytic processing of human host cell factor 1 (HCF-1) to its mature form was recently shown, unexpectedly, to occur in a UDP-GlcNAc-dependent fashion within the transferase active site of O-GlcNAc-transferase (OGT) (Lazarus, M. B., Jiang, J., Kapuria, V., Bhuiyan, T., Janetzko, J., Zandberg, W. F., Vocadlo, D. J., Herr, W., and Walker, S. (2013) Science 342, 1235-1239). An interesting mechanism involving formation and then intramolecular rearrangement of a covalent glycosyl ester adduct of the HCF-1 polypeptide was proposed to account for this unprecedented proteolytic activity. However, the key intermediate remained hypothetical. Here, using a model enzyme system for which the formation of a glycosyl ester within the enzyme active site has been shown unequivocally, we show that ester formation can indeed lead to proteolysis of the adjacent peptide bond, thereby providing substantive support for the mechanism of HCF-1 processing proposed.
authors.affiliation: From the Department of Chemistry, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada.
authors.forename: Miriam P
authors.initials: MP
authors.lastname: Kötzler
authors.affiliation: From the Department of Chemistry, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada withers@chem.ubc.ca.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Withers
mesh_terms: D001329:Autolysis; D005971:Glutamates / Q000378:metabolism; D006031:Glycosylation; D011489:Protein Denaturation; D011506:Proteins / Q000378:metabolism*; D059748:Proteolysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D001617:beta-Glucosidase / Q000378:metabolism
chemical_list: D005971:Glutamates; D011506:Proteins; D001617:beta-Glucosidase
keywords: glutamate; glutamyl ester; glycobiology; glycosidase; glycosyl ester; glycosylation; protein processing; protein splicing; proteolysis; pyroglutamate