CONSERVED STRUCTURAL FEATURES IN EUKARYOTIC AND PROKARYOTIC FUCOSYL-TRANSFERASES

Fucosyltransferases are the enzymes transferring fucose from GDP-Fuc t o Gal in an alpha 1,2-linkage and to GlcNAc in alpha 1,3-, alpha 1,4-, or alpha 1,6-linkages. Since all fucosyltransferases utilize the same nucleotide sugar, their specificity will probably reside in the recog nition of the acceptor and in the type of linkage formed, A search of nucleotide and protein databases yielded more than 30 sequences of fuc osyltransferases originating from mammals, chicken, nematode, and bact eria, On the basis of protein sequence similarities, these enzymes can be classified into four distinct families: (1) the alpha-2-fucosyltra nsferases, (2) the alpha-3-fucosyltransferases, (3) the mammalian alph a-6-fucosyltransferases, and (4) the bacterial alpha-6-fucosyltransfer ases. Nevertheless, using the sensitive hydrophobic cluster analysis ( HCA) method, conserved structural features as well as a consensus pept ide motif have been clearly identified in the catalytic domains of all alpha-2 and alpha-6-fucosyltranferases, from prokaryotic and eukaryot ic origin, that allowed the grouping of these enzymes into one superfa mily, In addition, a few amino acids were found strictly conserved in this family, and two of these residues have been reported to be essent ial for enzyme activity for a human alpha-2-fucosyltransferase. The al pha-3-fucosyltransferases constitute a distinct family as they lack th e consensus peptide, but some regions display similarities with the al pha-2 and alpha-6-fucosyltransferases. All these observations strongly suggest that the fucosyltransferases share some common structural and catalytic features.