Fold-recognition and comparative modeling of human β3GalT I, II, IV, V and VI and β3GalNAcT I: prediction of residues conferring acceptor substrate specificity

摘要

β3GalTs are type II transmembrane proteins that transfer galactose from UDP-Gal donor substrate to acceptor GlcNAc, GalNAc or Gal in β1 → 3-linkage. β1 → 3-linked galactose have been found to be a part of many glycans like glycosphingolipids, core tetrasaccharide of proteoglycans, type 1 chains. The 3-D structure of none of the β3GalTs is known to date. In this study, the 3-D structures of human β3GalT I, II, IV, V, VI and β3GalNAcT I have been modeled using fold-recognition and comparative modeling methods. Residues that constitute the UDP-Gal binding site have been predicted. The models are able to qualitatively rationalize data from the site-directed mutagenesis experiments reported in the literature. Residues likely to be involved in conferring differential acceptor substrate specificity have been predicted by a combination of specificity determining positions prediction (SDPs) and subsequent mapping on the generated 3-D models.