Sialic acid

About: Sialic acid is a research topic. Over the lifetime, 10929 publications have been published within this topic receiving 414624 citations. The topic is also known as: (4S,5R,6R,7S,8R)-5-acetamido-4,6,7,8,9-pentahydroxy-2-oxononanoic acid & sialic acid.

Diversity in the sialic acids

Abstract: Historical background It is now more than 50 years since N-acetyl-neuraminic acid was first discovered and subsequently characterized by several groups (reviewed in Roseman, 1970; Gottschalk, 1972; Rosenberg and Schengrund, 1976; Schauer, 1982; Faillard, 1989). Relatively soon after its discovery, it became apparent that this molecule was actually the major member of a family of compounds related to neuraminic acid that were christened the 'sialic acids' (Blix etai, 1957). Early studies paid close attention to the different types of sialic acids and the interrelationships between them. However, interest in these complexities subsequently waned and unpublished 'folk-lore' had it that modified sialic acids were species-specific curiosities found only in a few tissues, such as erythrocytes and submaxillary glands. In fact, many investigators in the 1970s and 80s used the terms W-acetyl-neuraminic acid' and 'sialic acid' synonymously. Thus, for example, when structural or biological changes were noted following treatments with a sialidase (neuraminidase), it was often assumed that the sialic acid released was A^-acetyl-neuraminic acid. It is now clear tjiat the different types of sialic acids are much more widely distributed than previously thought. This review attempts to briefly summarize current knowledge concerning the occurrence, structure, biochemistry and biological significance of this diversity in the sialic acids. Particular attention is given to the two most common and better studied modifications: the addition of 0-acetyl esters to the hydroxyl groups at the 4-, 7-, 8- and 9-positions, and the conversion of the 7V-acetyl group to an /V-glycolyl group. Given the breadth of the review, the bibliography is only representative, and tends to emphasize more recent studies.

Receptor and ligand domains for invasion of erythrocytes by Plasmodium falciparum

Abstract: A 175-kilodalton erythrocyte binding protein, EBA-175, of the parasite Plasmodium falciparum mediates the invasion of erythrocytes. The erythrocyte receptor for EBA-175 is dependent on sialic acid. The domain of EBA-175 that binds erythrocytes was identified as region II with the use of truncated portions of EBA-175 expressed on COS cells. Region II, which contains a cysteine-rich motif, and native EBA-175 bind specifically to glycophorin A, but not to glycophorin B, on the erythrocyte membrane. Erythrocyte recognition of EBA-175 requires both sialic acid and the peptide backbone of glycophorin A. The identification of both the receptor and ligand domains may suggest rational designs for receptor blockade and vaccines.

Crystal structure of cholera toxin B‐pentamer bound to receptor GM1 pentasaccharide

Abstract: Cholera toxin (CT) is an AB5 hexameric protein responsible for the symptoms produced by Vibrio cholerae infection. In the first step of cell intoxication, the B-pentamer of the toxin binds specifically to the branched pentasaccharide moiety of ganglioside GM1 on the surface of target human intestinal epithelial cells. We present here the crystal structure of the cholera toxin B-pentamer complexed with the GM1 pentasaccharide. Each receptor binding site on the toxin is found to lie primarily within a single B-subunit, with a single solvent-mediated hydrogen bond from residue Gly 33 of an adjacent subunit. The large majority of interactions between the receptor and the toxin involve the 2 terminal sugars of GM1, galactose and sialic acid, with a smaller contribution from the N-acetyl galactosamine residue. The binding of GM1 to cholera toxin thus resembles a 2-fingered grip: the Gal(beta 1-3)GalNAc moiety representing the "forefinger" and the sialic acid representing the "thumb." The residues forming the binding site are conserved between cholera toxin and the homologous heat-labile enterotoxin from Escherichia coli, with the sole exception of His 13. Some reported differences in the binding affinity of the 2 toxins for gangliosides other than GM1 may be rationalized by sequence differences at this residue. The CTB5:GM1 pentasaccharide complex described here provides a detailed view of a protein:ganglioside specific binding interaction, and as such is of interest not only for understanding cholera pathogenesis and for the design of drugs and development of vaccines but also for modeling other protein:ganglioside interactions such as those involved in GM1-mediated signal transduction.

Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid

Abstract: Humans are genetically unable to produce the sialic acid N-glycolylneuraminic acid (Neu5Gc), because of a mutation that occurred after our last common ancestor with great apes. Although Neu5Gc is presumed absent from normal humans, small amounts have been claimed to exist in human tumors and fetal meconium. We have generated an antibody with high specificity and avidity for Neu5Gc. Fetal tissues, normal adult tissues, and breast carcinomas from humans showed reactivity to this antibody, primarily within secretory epithelia and blood vessels. The presence of small amounts of Neu5Gc was confirmed by MS. Absent any known alternate pathway for its synthesis, we reasoned that these small amounts of Neu5Gc might originate from exogenous sources. Indeed, human cells fed with Neu5Gc incorporated it into endogenous glycoproteins. When normal human volunteers ingested Neu5Gc, a portion was absorbed and eliminated in urine, and small quantities were incorporated into newly synthesized glycoproteins. Neu5Gc has never been reported in plants or microbes to our knowledge. We found that Neu5Gc is rare in poultry and fish, common in milk products, and enriched in red meats. Furthermore, normal humans have variable amounts of circulating IgA, IgM, and IgG antibodies against Neu5Gc, with the highest levels comparable to those of the previously known anti-α-galactose xenoreactive antibodies. This finding represents an instance wherein humans absorb and metabolically incorporate a nonhuman dietary component enriched in foods of mammalian origin, even while generating xenoreactive, and potentially autoreactive, antibodies against the same molecule. Potential implications for human diseases are briefly discussed.

Perspectives on the significance of altered glycosylation of glycoproteins in cancer

Abstract: No abstract Abbreviations:Sia, sialic acid, type unspecified; Tn antigen, GalNAcα 1-O-Ser/Thr; T antigen, Galβ1-3GalNAcα-O-Ser/Thr; Sialyl LewisX, Siaα2-3Galβ1-4(Fucα1-3)GlcNAc; Sialyl Lewisa, Siaα2-3Galβ1-3(Fucα1-4)GlcNAc; Sialyl-Tn antigen, Siaα2-6GalNAcα1-O-Ser/Thr; FucT, fucosyltransferase; ST, sialyltransferase.