Abstract
UDP-GalNAc:polypeptide GalNAc transferase (ppGalNAcT; EC 2.4.1.41) is the initiating enzyme for mucin-type O-glycosylation in animals. Members of this highly conserved glycosyltransferase family catalyse a single glycosidic linkage. They transfer an N-acetylgalactosamine (GalNAc) residue from an activated donor (UDP-GalNAc) to a serine or threonine of an acceptor polypeptide chain. A ppGalNAcT from the freshwater snail Biomphalaria glabrata is the only characterised member of this enzyme family from mollusc origin. In this work, we interpret previously published experimental characterization of this enzyme in the context of in silico models of the enzyme and its acceptor substrates. A homology model of the mollusc ppGalNAcT is created and various substrate peptides are modelled into the active site. We hypothesize about possible molecular interpretations of the available experimental data and offer potential explanations for observed substrate and cofactor specificity. Here, we review and synthesise the current knowledge of Bge-ppGalNAcT, supported by a molecular interpretation of the available data.
Highlights
UDP-GalNAc:polypeptide GalNAc transferases [EC 2.4.1.41]) is the initiating enzyme for mucintype O-glycosylation
In invertebrates homologous enzymes have been described in insects (Drosophila melanogaster, Bombyx mori), worms (Caenorhabditis elegans, Fasciola hepática, Echinococcus granulosus), parasites (Toxoplasma gondi, Trypanosoma cruzi, Cryptosporidium species) and the purple sea urchin (Stronglylocetrotus purpuratus) [6,7,8,9,10,11,12,13,14,15,16], but never in bacteria, plants or fungi
Biomphalaria glabrata ppGalNAcT is homologous to human ppGalNAcT2 with 61% sequence identity when the 4D0T structure is used as a template with 94% coverage; using 2FFV it is 65% sequence identity, with 82% coverage (Fig. 1)
Summary
UDP-GalNAc:polypeptide GalNAc transferases [EC 2.4.1.41]) (ppGalNAcT) is the initiating enzyme for mucintype O-glycosylation. Glycoconj J (2020) 37:15–25 characterised member of this enzyme family from mollusc origin [17, 18] The members of this enzyme family (CAZy1 glycosyltransferase family 27) are type II transmembrane proteins that share common structural features: a short N-terminal cytoplasmic tail, followed by the transmembrane region, a stem section, a first catalytic domain (subdomain A) containing a substrate and a manganese binding site, a second catalytic domain (subdomain B) containing the Gal/GalNAc motif responsible for binding of UDP-GalNAc, a flexible linker, and a ricin-like lectin domain with a β-trefoil fold built from three repeat units at the C-terminus [2]. We show the structural modelling of the mollusc ppGalNAcT from Biomphalaria glabrata (BgeppGalNAcT), comparing the snail enzyme and the well investigated homologous human ppGalNAcT2 with a focus on structural similarities and differences. We consider this work as a review and synthesis of the current knowledge of Bge-ppGalNAcT, supported by a molecular interpretation of the available data
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
