Glycosyltransferases are enzymes (EC 2.4) that act as a catalyst for the transfer of a monosaccharide unit from an activated sugar phosphate (known as the "glycosyl donor") to an acceptor molecule, usually an alcohol.
The result of glycosyl transfer can be a monosaccharide glycoside, an oligosaccharide, or a polysaccharide, although some glycosyltransferases catalyse transfer to inorganic phosphate or water. Glycosyl transfer can also occur to protein residues, usually to tyrosine, serine or threonine to give O-linked glycoproteins, or to asparagine to give N-linked glycoproteins. Mannosyl groups may be transferred to tryptophan to generate C-mannosyl tryptophan, which is relatively abundant in eukaryotes.
Commonly, sugar nucleotide derivatives are used as glycosyl donors. Glycosyltransferases that use sugar nucleotides are called Leloir enzymes, after Luis F. Leloir, the scientist who discovered the first sugar nucleotide and who received the 1970 Nobel Prize in Chemistry for his work on carbohydrate metabolism.
Glycosyltransferases that utilize non-nucleotide donors, which may be polyprenol pyrophosphates, polyprenol phosphates, sugar-1-phosphates or sugar-1-pyrophosphates, are termed non-Leloir glycosyltransferases. Such non-Leloir enzymes occur in a variety of organisms.
Mammals utilize only 9 sugar nucleotide donors for glycosyltransferases: UDP-glucose, UDP-galactose, UDP-GlcNAc, UDP-GalNAc, UDP-xylose, UDP-glucuronic acid, GDP-mannose, GDP-fucose, and CMP-sialic acid. Other organisms have an extensive range of sugar nucleotide donors. Many glycosyltransferases in a number of organisms use lipid linked glycosyl donors where the lipid is frequently a terpenoid such as dolichol or polyprenol.
Sequence based classification methods have proven to be a powerful way of generating hypotheses for protein function based on sequence alignment to related proteins. The carbohydrate active enzyme database presents a sequence based classification of glycosyltransferases into over 86 families. The same three-dimensional fold is expected to occur within each of the families.
In contrast to the diversity of 3D structures observed for glycoside hydrolases, glycosyltransferase have a much smaller range of structures. In fact, according to the Structural Classification of Proteins" database only three different folds have been observed for glycosyltransferases Very recently, a new glycosyltransferase fold was identified for the glycosyltransferases involved in the biosynthesis of the NAG-NAM polymer backbone of peptidoglycan.
Many inhibitors of glycosyltransferases are known. Some of these are natural products, such as moenomycin, an inhibitor of peptidoglycan glycosyltransferases, the nikkomycins, inhibitors of chitin synthase, and the echinocandins, inhibitors of fungal b-1,3-glucan synthases. Some glycosyltransferase inhibitors are of use as drugs or antibiotics. Moenimycin is used in animal feed as a growth promoter. Caspofungin has been developed from the echinocandins and is in use as an antifungal agent. Ethambutol is an inhibitor of mycobacterial arabinotransferases and is used for the treatment of tuberculosis. Lufenuron is an inhibitor of insect chitin synthases and is used to control fleas in animals.
Glycosyltransferases have been widely used in the synthesis of glycoconjugates. Suitable enzymes can be isolated from natural sources or produced recombinantly. Alternatively, whole cell based systems utilizing either endogenous glycosyl donors or cell based systems containing cloned and expressed systems for synthesis of glycosyl donors have been developed. In cell-free approaches the large scale application of glycosyltransferases for glycoconjugate synthesis has required access to large quantities of the glycosyl donors. Alternatively, nucleotide recycling systems have been developed that allow the resynthesis of glycosyl donors from the released nucleotide. The nucleotide recycling approach has a further benefit of reducing the amount of nucleotide formed as a by-product, thereby reducing the amount of inhibition caused to the glycosyltransferase of interest - a commonly observed feature of the nucleotide byproduct.
WIPO ASSIGNS PATENT TO NATIONAL UNIVERSITY CORPORATION TOKYO UNIVERSITY OF AGRICULTURE AND TECHNOLOGY FOR "NOVEL GLYCOSYLTRANSFERASE, NOVEL GLYCOSYLTRANSFERASE GENE, AND NOVEL GLYCOSYL DONOR COMPOUND" (JAPANESE INVENTORS)
Feb 16, 2011; GENEVA, Feb. 16 -- Publication No. WO/2011/016260 was published on Feb. 10. Title of the invention: "NOVEL...
WIPO PUBLISHES PATENT OF RESEARCH AND DIAGNOSTIC SYSTEMS FOR "PHOSPHATASE COUPLED GLYCOSYLTRANSFERASE ASSAY" (AMERICAN INVENTOR)
Dec 07, 2011; GENEVA, Dec. 5 -- Publication No. WO/2011/149448 was published on Dec. 01. Title of the invention: "PHOSPHATASE COUPLED...