Comparative sequence analysis in the sialyltransferase protein family: analysis of motifs.
The sialyltransferase family represents a group of enzymes that transfers sialic acid from its common nucleotide sugar donor, CMP-NeuAc, to the terminal carbohydrates group of various glycoproteins and glycolipids. Cloning of these enzymes from mammalian sources indicated these are all type II membrane proteins with topological features common to other glycosyltransferases. To date, 20 cloned enzymes with distinct substrate specificity have been obtained for mammalian sialyltransferases. These account for four subfamilies according to the carbohydrate linkages synthesized, namely, ST3Gal, ST6Gal, ST6GalNAc, and ST8Sia. Comparative peptide sequence analysis of these cloned enzymes showed the presence of four conserve sialylmotifs, namely 'L'- (for long), 'S'- (for short), -'III' (for being third position in sequence) and '-VS' (for very small), common to all of this protein family. Experiments by site-directed mutagenesis showed evidence that these motifs contribute to the binding of either donor or the acceptor or both. While the L-sialylmotif contributes to the binding of the donor substrate, the motifs -III and -VS contribute to the binding of the acceptor substrate. S-sialymotif, on the other hand, contributes to the binding of both the donor and acceptor substrates. Apparently, a disulfide linkage between the L-sialylmotif and the S-sialylmotif bringing all of these motifs closer together facilitates such interaction with the substrates. In addition, although with no experimental evidence, comparative sequence analysis also suggests a strong correlation of linkage specificity of these enzymes with the peptide sequence closer to these sialylmotifs.
Datta
Arun K
AK
National University, San Diego, CA, USA. adatta@nu.edu
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D054730:Protein Interaction Domains and Motifs; D017386:Sequence Homology, Amino Acid; D012799:Sialyltransferases / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity
D012799:Sialyltransferases