Oligosaccharide branching of glycoproteins: biosynthetic mechanisms and possible biological functions. 1982

H Schachter, and S Narasimhan, and P Gleeson, and G J Vella, and I Brockhausen

One of the most striking features of N- and O-glycosyl oligosaccharides and of lipid-linked oligosaccharides is the high degree of branching of these complex structures. Both proteins and nucleic acids are essentially linear structures and are synthesized by template mechanisms. The branched nature of complex carbohydrates dictates a totally different mechanism of biosynthetic control. Although there are undoubtedly many factors controlling this assembly (e.g. subcellular compartmentation, availability of substrates, cations), our laboratory has studied primarily the enzymatic factors that control the assembly of branched N-glycosyl (Asn-GlcNAc type) and O-glycosyl (Ser[Thr]-GalNAc type) oligosaccharides. There are three basic types of control points that appear to direct biosynthesis. (a) There may be two or more enzymes capable of acting on a single common substrate. Control at this juncture is exerted by the relative activities of these enzymes in a particular tissue. (b) Addition of a specific sugar to the growing oligosaccharide may shut off one or more subsequent enzyme steps, thereby 'freezing' the structure at a certain stage in its synthesis. (c) Progression of the pathway may be impossible until a certain key sugar residue is inserted into the growing oligosaccharide chain. Examples of all three types of control occur in the assembly of both N- and O-glycosyl oligosaccharides. This paper discusses our work on the N-acetylglucosaminyltransferases, which initiate branches in N-glycosyl oligosaccharides, as well as some studies on glycosyltransferases that control the assembly of the four basic Ser(Thr)-GalNAc cores. Important features at all stages of control are the three-dimensional shape of the oligosaccharide, the effect of certain key sugar residues on this three-dimensional shape and the stereochemistry of the interaction of oligosaccharides with proteins. From a functional point of view, protein-oligosaccharide interaction is of vital importance not only to enzyme control mechanisms but to a variety of biological problems such as malignancy and cell-cell interactions, differentiation and development, and susceptibility of cells to hormones, drugs and toxins.

UI MeSH Term Description Entries
D009077 Mucins High molecular weight mucoproteins that protect the surface of EPITHELIAL CELLS by providing a barrier to particulate matter and microorganisms. Membrane-anchored mucins may have additional roles concerned with protein interactions at the cell surface. Mucin
D009844 Oligosaccharides Carbohydrates consisting of between two (DISACCHARIDES) and ten MONOSACCHARIDES connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. Oligosaccharide
D011499 Protein Processing, Post-Translational Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility. Amino Acid Modification, Post-Translational,Post-Translational Modification,Post-Translational Protein Modification,Posttranslational Modification,Protein Modification, Post-Translational,Amino Acid Modification, Posttranslational,Post-Translational Amino Acid Modification,Post-Translational Modifications,Post-Translational Protein Processing,Posttranslational Amino Acid Modification,Posttranslational Modifications,Posttranslational Protein Processing,Protein Processing, Post Translational,Protein Processing, Posttranslational,Amino Acid Modification, Post Translational,Modification, Post-Translational,Modification, Post-Translational Protein,Modification, Posttranslational,Modifications, Post-Translational,Modifications, Post-Translational Protein,Modifications, Posttranslational,Post Translational Amino Acid Modification,Post Translational Modification,Post Translational Modifications,Post Translational Protein Modification,Post Translational Protein Processing,Post-Translational Protein Modifications,Processing, Post-Translational Protein,Processing, Posttranslational Protein,Protein Modification, Post Translational,Protein Modifications, Post-Translational
D002240 Carbohydrate Sequence The sequence of carbohydrates within POLYSACCHARIDES; GLYCOPROTEINS; and GLYCOLIPIDS. Carbohydrate Sequences,Sequence, Carbohydrate,Sequences, Carbohydrate
D006023 Glycoproteins Conjugated protein-carbohydrate compounds including MUCINS; mucoid, and AMYLOID glycoproteins. C-Glycosylated Proteins,Glycosylated Protein,Glycosylated Proteins,N-Glycosylated Proteins,O-Glycosylated Proteins,Glycoprotein,Neoglycoproteins,Protein, Glycosylated,Proteins, C-Glycosylated,Proteins, Glycosylated,Proteins, N-Glycosylated,Proteins, O-Glycosylated
D006602 Hexosyltransferases Enzymes that catalyze the transfer of hexose groups. EC 2.4.1.-.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001216 Asparagine A non-essential amino acid that is involved in the metabolic control of cell functions in nerve and brain tissue. It is biosynthesized from ASPARTIC ACID and AMMONIA by asparagine synthetase. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed) L-Asparagine
D012694 Serine A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids. L-Serine,L Serine
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog

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