Chemical Diversity in the Sialic Acids and Related α-Keto Acids: An Evolutionary Perspective

Capsules are protective structures on the surfaces of many bacteria. The remarkable structural diversity in capsular polysaccharides is illustrated by almost 80 capsular serotypes in Escherichia coli. Despite this variation, the range of strategies used for capsule biosynthesis and assembly is limited, and E. coli isolates provide critical prototypes for other bacterial species. Related pathways are also used for synthesis and export of other bacterial glycoconjugates and some enzymes/processes have counterparts in eukaryotes. In gram-negative bacteria, it is proposed that biosynthesis and translocation of capsular polysaccharides to the cell surface are temporally and spatially coupled by multiprotein complexes that span the cell envelope. These systems have an impact on both a general understanding of membrane trafficking in bacteria and on bacterial pathogenesis.

Biosynthesis and Assembly of Capsular Polysaccharides in Escherichia coli

It is well established that high doses of monomeric immunoglobulin G (IgG) purified from pooled human plasma [intravenous immunoglobulin (IVIG)] confer anti-inflammatory activity in a variety of autoimmune settings. However, exactly how those effects are mediated is not clear because of the heterogeneity of IVIG. Recent studies have demonstrated that the anti-inflammatory activity of IgG is completely dependent on sialylation of the N-linked glycan of the IgG Fc fragment. Here we determine the precise glycan requirements for this anti-inflammatory activity, allowing us to engineer an appropriate IgG1 Fc fragment, and thus generate a fully recombinant, sialylated IgG1 Fc with greatly enhanced potency. This therapeutic molecule precisely defines the biologically active component of IVIG and helps guide development of an IVIG replacement with improved activity and availability.

https://science.sciencemag.org/content/sci/320/5874/373.full.pdf

Recapitulation of IVIG Anti-Inflammatory Activity with a Recombinant IgG Fc

Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, glycoproteins, and proteoglycans, the compositions of which vary among different tissues and cell types. Many of the linear and branched glycans on cell surface glycoproteins and glycolipids of vertebrates are terminated with sialic acids, nine-carbon sugars with a carboxylic acid, a glycerol side-chain, and an N-acyl group that, along with their display at the outmost end of cell surface glycans, provide for varied molecular interactions. Among their functions, sialic acids regulate cell-cell interactions, modulate the activities of their glycoprotein and glycolipid scaffolds as well as other cell surface molecules, and are receptors for pathogens and toxins. In the brain, two families of sialoglycans are of particular interest: gangliosides and polysialic acid. Gangliosides, sialylated glycosphingolipids, are the most abundant sialoglycans of nerve cells. Mouse genetic studies and human disorders of ganglioside metabolism implicate gangliosides in axon-myelin interactions, axon stability, axon regeneration, and the modulation of nerve cell excitability. Polysialic acid is a unique homopolymer that reaches >90 sialic acid residues attached to select glycoproteins, especially the neural cell adhesion molecule in the brain. Molecular, cellular, and genetic studies implicate polysialic acid in the control of cell-cell and cell-matrix interactions, intermolecular interactions at cell surfaces, and interactions with other molecules in the cellular environment. Polysialic acid is essential for appropriate brain development, and polymorphisms in the human genes responsible for polysialic acid biosynthesis are associated with psychiatric disorders including schizophrenia, autism, and bipolar disorder. Polysialic acid also appears to play a role in adult brain plasticity, including regeneration. Together, vertebrate brain sialoglycans are key regulatory components that contribute to proper development, maintenance, and health of the nervous system.

https://www.physiology.org/doi/pdf/10.1152/physrev.00033.2013

Sialic Acids in the Brain: Gangliosides and Polysialic Acid in Nervous System Development, Stability, Disease, and Regeneration

Pathways of O-glycan biosynthesis in cancer cells.

The sialyltransferase sialylmotif participates in binding the donor substrate cmp-neuac

Laboratory for Molecular Glycobiology, Frontier Research Program, TheInstitute of Physical and Chemical Research (RIKEN), Wako, Saitama,351 01, Japan and 'Cytel Corporation and the Department of Chemistry andMolecular Biology, Scnpps Research Institute, 3525 John Hopkins Court,San Diego, CA 92121, US A

Systematic nomenclature for sialyltransferases

/pdf/efficient-amplification-using-megaprimer-by-asymmetric-xur2did1i3.pdf

Arun K. Datta

Papers

The sialyltransferase sialylmotif participates in binding the donor substrate cmp-neuac

Systematic nomenclature for sialyltransferases

Efficient amplification using 'megaprimer' by asymmetric polymerase chain reaction.

Mutation of the sialyltransferase S-sialylmotif alters the kinetics of the donor and acceptor substrates.

Conserved cysteines in the sialyltransferase sialylmotifs form an essential disulfide bond.