A beta-1,3-N-acetylglucosaminyltransferase with poly-N-acetyllactosamine synthase activity is structurally related to beta-1,3-galactosyltransferases

Human and mouse cDNAs encoding a new beta-1,3-N-acetylglucosaminyltransfera se (beta 3GnT) have been isolated from fetal and newborn brain libraries. T he human and mouse cDNAs included ORFs coding for predicted type II transme mbrane polypeptides of 329 and 325 aa, respectively. The human and mouse be ta 3GnT homologues shared 90% similarity. The beta 3GnT gene was widely exp ressed in human and mouse tissues, although differences in the transcript l evels were visible, thus indicating possible tissue-specific regulation mec hanisms. The beta 3GnT enzyme showed a marked preference for Gal(beta 1-4)G lc(NAc)-based accepters, whereas no activity was detected on type 1 Gal(bet a 1-3)GlcNAc and O-glycan core 1 Gal(beta 1-3)GalNAc accepters, The new bet a 3GnT enzyme was capable of both initiating and elongating poly-N-acetylla ctosamine chains, which demonstrated its identity with the poly-N-acetyllac tosamine synthase enzyme (E.C. 2.4.1.149), showed no similarity with the i antigen beta 3GnT enzyme described recently, and, strikingly, included seve ral amino acid motifs in its protein that have been recently identified in beta-1,3-galactosyltransferase enzymes. The comparison between the new UDP- GlcNAc:beta Gal beta 3GnT and the three UDP-Gal:beta GlcNAc beta-1,3-galact osyltransferases-I, -II, and -III reveals glycosyltransferases that share c onserved sequence motifs though exhibiting inverted donor and acceptor spec ificities. This suggests that the conserved amino acid motifs likely repres ent residues required for the catalysis of the glycosidic (beta 1-3) linkag e.