Disease relevance of B4GALT1

• The high-resolution X-ray crystal structures of a new form of bacteriophage T4 beta-glucosyltransferase, Escherichia coli MurG, Bacillus subtilis SpsA, bovine beta-1,4-galactosyltransferase 1 and rabbit N-acetylglucosaminyltransferase I have now been solved [1].
• Baculovirus infection of the transformed cells stimulated beta 1,4-galactosyltransferase activity almost 5-fold by 12 h postinfection [2].
• These compounds proved not to be inhibitors of bovine beta-1,4-galactosyltransferase although some showed moderate inhibition of Salmonella dTDP-alpha-D-glucose 4,6-dehydratase (RmlB) [3].

High impact information on B4GALT1

• Here we solved and refined the crystal structures of recombinant bovine beta4Gal-T1 to 2.4 A resolution in the presence and absence of the substrate uridine diphosphogalactose [4].
• The crystal structure of the bovine substrate-free beta4Gal-T1 catalytic domain showed a new fold consisting of a single conical domain with a large open pocket at its base [4].
• In mammals, beta4Gal-T1 binds to alpha-lactalbumin, a protein that is structurally homologous to lyzozyme, to produce lactose. beta4Gal-T1 is a member of a large family of homologous beta4galactosyltransferases that use different types of glycoproteins and glycolipids as substrates [4].
• These results help the interpretation of engineered beta4Gal-T1 point mutations [4].
• Expression of bovine beta-1,4-galactosyltransferase cDNA in COS-7 cells [5].

Chemical compound and disease context of B4GALT1

• A number of N- and C-terminal deletion and point mutants of bovine beta-1,4 galactosyltransferase (beta-1,4GT) were expressed in E. coli to determine the binding regions of the enzyme that interact with N-acetylglucosamine (NAG) and UDP-galactose [6].

Biological context of B4GALT1

• Crystallographic studies on bovine beta4Gal-T1 have shown that the primary metal binding site is located in the hinge region of a long flexible loop, which upon Mn(2+) and UDP-Gal binding changes from an open to a closed conformation [7].
• Flexibility in the donor substrate specificity of beta 1,4-galactosyltransferase: application in the synthesis of complex carbohydrates [8].
• An established lepidopteran insect cell line (Sf9) was cotransfected with expression plasmids encoding neomycin phosphotransferase and bovine beta 1,4-galactosyltransferase [2].
• A combined rational and library approach was used to identify bisphosphonates (IC50 = 20 microM) and galactose type 1-N-iminosugar (IC50=45 microM) as novel motifs for selective inhibition of beta-1,4-galactosyltransferase (beta-1,4-GalT) and alpha-1,3-galactosyltransferase (alpha-1,3-GalT), respectively [9].

Anatomical context of B4GALT1

• Branch specificity of bovine colostrum and calf thymus UDP-Gal: N-acetylglucosaminide beta-1,4-galactosyltransferase [10].
• We previously described a transgenic insect cell line, Sfbeta4GalT/ST6, that expresses mammalian beta-1,4-galactosyltransferase and alpha2,6-sialyltransferase genes and produces glycoproteins with terminally sialylated N-glycans [11].
• The beta 1,4GalNAcT in CHO cells is distinct from beta 1,4 galactosyltransferase in that the latter enzyme, but not the former, binds to a column of immobilized bovine alpha-lactalbumin [12].
• In recent years, we have exploited the regioselectivity of lipases and proteases in organic solvents for the synthesis of specific esters of ginsenosides as well as the selectivity of the beta-1,4-galactosyltransferase from bovine colostrum to obtain new glycosyl derivatives of these compounds [13].

Associations of B4GALT1 with chemical compounds

• LA promotes the binding of glucose (Glc) to beta4Gal-T1, thereby altering its sugar acceptor specificity from N-acetylglucosamine (GlcNAc) to glucose, which enables LS to synthesize lactose, the major carbohydrate component of milk [14].
• Thus, the role of LA is to hold Glc by hydrogen bonding with the O-1 hydroxyl group in the acceptor-binding site on beta4Gal-T1, while the N-acetyl group-binding pocket in beta4Gal-T1 adjusts to maximize the interactions with the Glc molecule [14].
• Effect of the Met344His mutation on the conformational dynamics of bovine beta-1,4-galactosyltransferase: crystal structure of the Met344His mutant in complex with chitobiose [7].
• Beta-1,4-galactosyltransferase (beta4Gal-T1) in the presence of manganese ion transfers galactose from UDP-galactose (UDP-Gal) to N-acetylglucosamine (GlcNAc) that is either free or linked to an oligosaccharide [7].
• Synthesis of poly-N-acetyllactosamine in core 2 branched O-glycans. The requirement of novel beta-1,4-galactosyltransferase IV and beta-1,3-n-acetylglucosaminyltransferase [15].

References