Biomaterial Database

Recognition of beta-D-Gal p-(1-->3)-beta-D-Glc pNAc-OR acceptor analogues by the Lewis alpha-(1-->3/4)-fucosyltransferase from human milk. 1996

M Du, and O Hindsgaul

Department of Chemistry, University of Alberta, Edmonton, Canada.

The Lewis alpha-(1-->3/4)-fucosyltransferase (E.C. 2.4.1.65) transfers L-fucose from GDP-fucose to OH-4 of the Glc pNAc residue in the disaccharide beta-D-Galp-(1-->3)-beta-D-Glc pNAc-OR [R = (CH2)8COOMe] (1) to give the Lewis-A blood group determinant beta-D-Gal p-(1-->3)-[alpha-L-Fuc p-(1-->4)]-beta-D-Glc pNAc-OR. Five deoxy analogous of 1, as well as its N-propionyl derivative, were chemically synthesized and kinetically evaluated as both substrates and inhibitors for the enzyme from human milk. The unmodified acceptor 1 had Km = 640 microM with Vmax set arbitrarily to 100. The 6-deoxy (Km = 400 microM, V(max) = 90) and N-propionyl compounds (Km = 330 microM, V(max) = 170) remained excellent substrates while the 4-deoxy compound was a very weak competitive inhibitor with Ki = 9 mM. Deoxygenation of OH-2' and OH-4'(of the Gal residue) in 1 had little effect on the activity. The OH-6 group of the Gal residue proved to be critical for recognition by the enzyme since substitution of this group with hydrogen led to an inactive compound.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008895	Milk, Human	Milk that is produced by HUMAN MAMMARY GLANDS.	Breast Milk,Human Milk,Milk, Breast
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D002240	Carbohydrate Sequence	The sequence of carbohydrates within POLYSACCHARIDES; GLYCOPROTEINS; and GLYCOLIPIDS.	Carbohydrate Sequences,Sequence, Carbohydrate,Sequences, Carbohydrate
D004187	Disaccharides	Oligosaccharides containing two monosaccharide units linked by a glycosidic bond.	Disaccharide
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005643	Fucose	A six-member ring deoxysugar with the chemical formula C6H12O5. It lacks a hydroxyl group on the carbon at position 6 of the molecule.	Deoxygalactose,alpha-Fucose,alpha Fucose
D005647	Fucosyltransferases	Enzymes catalyzing the transfer of fucose from a nucleoside diphosphate fucose to an acceptor molecule which is frequently another carbohydrate, a glycoprotein, or a glycolipid molecule. Elevated activity of some fucosyltransferases in human serum may serve as an indicator of malignancy. The class includes EC 2.4.1.65; EC 2.4.1.68; EC 2.4.1.69; EC 2.4.1.89.	Fucosyltransferase
D005697	Galactosides	Glycosides formed by the reaction of the hydroxyl group on the anomeric carbon atom of galactose with an alcohol to form an acetal. They include both alpha- and beta-galactosides.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man