Dataset Information

Bovine alpha1,3-galactosyltransferase catalytic domain structure and its relationship with ABO histo-blood group and glycosphingolipid glycosyltransferases.

ABSTRACT: alpha1,3-galactosyltransferase (alpha3GalT, EC 2.4.1.151) is a Golgi-resident, type II transmembrane protein that transfers galactose from UDP-alpha-galactose to the terminal N:-acetyllactosamine unit of glycoconjugate glycans, producing the Galalpha1,3Galbeta1,4GlcNAc oligosaccharide structure present in most mammalian glycoproteins. Unlike most other mammals, humans and Old World primates do not possess alpha3GalT activity, which is relevant for the hyperacute rejection observed in pig-to-human xenotransplantation. The crystal structure of the catalytic domain of substrate-free bovine alpha3GalT, solved and refined to 2.3 A resolution, has a globular shape with an alpha/beta fold containing a narrow cleft on one face, and shares a UDP-binding domain (UBD) with the recently solved inverting glycosyltransferases. The substrate-bound complex, solved and refined to 2.5 A, allows the description of residues interacting directly with UDP-galactose. These structural data suggest that the strictly conserved residue E317 is likely to be the catalytic nucleophile involved in galactose transfer with retention of anomeric configuration as accomplished by this enzyme. Moreover, the alpha3GalT structure helps to identify amino acid residues that determine the specificities of the highly homologous ABO histo-blood group and glycosphingolipid glycosyltransferases.

SUBMITTER: Gastinel LN

PROVIDER: S-EPMC145412 | biostudies-literature | 2001 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bovine alpha1,3-galactosyltransferase catalytic domain structure and its relationship with ABO histo-blood group and glycosphingolipid glycosyltransferases.

Gastinel L N LN Bignon C C Misra A K AK Hindsgaul O O Shaper J H JH Joziasse D H DH

The EMBO journal 20010201 4

alpha1,3-galactosyltransferase (alpha3GalT, EC 2.4.1.151) is a Golgi-resident, type II transmembrane protein that transfers galactose from UDP-alpha-galactose to the terminal N:-acetyllactosamine unit of glycoconjugate glycans, producing the Galalpha1,3Galbeta1,4GlcNAc oligosaccharide structure present in most mammalian glycoproteins. Unlike most other mammals, humans and Old World primates do not possess alpha3GalT activity, which is relevant for the hyperacute rejection observed in pig-to-huma ...[more]

PMID: 11179209

Similar Datasets

Project description:Some viruses within the Caliciviridae family initiate their replication cycle by attachment to cell surface carbohydrate moieties, histo-blood group antigens (HBGAs), and/or terminal sialic acids (SAs). Although bovine nebovirus (BNeV), one of the enteric caliciviruses, is an important causative agent of acute gastroenteritis in cattle, its attachment factors and possibly other cellular receptors remain unknown. Using a comprehensive series of protein-ligand biochemical assays, we sought to determine whether BNeV recognizes cell surface HBGAs and/or SAs as attachment factors. It was found that BNeV virus-like particles (VLPs) bound to A type/H type 2/Ley HBGAs expressed in the bovine digestive tract and are related to HBGAs expressed in humans and other host species, suggesting a wide spectrum of HBGA recognition by BNeV. BNeV VLPs also bound to a large variety of different bovine and human saliva samples of all ABH and Lewis types, supporting previously obtained results and suggesting a zoonotic potential of BNeV transmission. Removal of ?1,2-linked fucose and ?1,3/4-linked fucose epitopes of target HBGAs by confirmation-specific enzymes reduced the binding of BNeV VLPs to synthetic HBGAs, bovine and human saliva, cultured cell lines, and bovine small intestine mucosa, further supporting a wide HBGA binding spectrum of BNeV through recognition of ?1,2-linked fucose and ?1,3/4-linked fucose epitopes of targeted HBGAs. However, removal of terminal ?2,3- and ?2,6-linked SAs by their specific enzyme had no inhibitory effects on binding of BNeV VLPs, indicating that BNeV does not use terminal SAs as attachment factors. Further details of the binding specificity of BNeV remain to be explored.IMPORTANCE Enteric caliciviruses such as noroviruses, sapoviruses, and recoviruses are the most important etiological agents of severe acute gastroenteritis in humans and many other mammalian host species. They initiate infection by attachment to cell surface carbohydrate moieties, HBGAs, and/or terminal SAs. However, the attachment factor(s) for BNeV, a recently classified enteric calicivirus genus/type species, remains unexplored. Here, we demonstrate that BNeV VLPs have a wide spectrum of binding to synthetic HBGAs, bovine and human saliva samples, and bovine duodenal sections. We further discovered that ?1,2-linked fucose and ?1,3/4-linked fucose epitopes are essential for binding of BNeV VLPs. However, BNeV VLPs do not bind to terminal SAs on cell carbohydrates. Continued investigation regarding the proteinaceous receptor(s) will be necessary for better understanding of the tropism, pathogenesis, and host range of this important viral genus.

Dataset Information

Bovine alpha1,3-galactosyltransferase catalytic domain structure and its relationship with ABO histo-blood group and glycosphingolipid glycosyltransferases.

Publications

Bovine alpha1,3-galactosyltransferase catalytic domain structure and its relationship with ABO histo-blood group and glycosphingolipid glycosyltransferases.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets