High-resolution proton NMR studies of gangliosides. 1. Use of homonuclear two-dimensional spin-echo J-correlated spectroscopy for determination of residue composition and anomeric configurations

Koerner, Theodore A.W.; Prestegard, James H.; Demou, Peter C.; Yu, Robert K.

doi:10.1021/bi00280a014

Cited by 219 publications

(96 citation statements)

References 32 publications

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“…The individual glycosphingolipids were isolated by acetylation of the total glycosphingolipid fractions and repeated chromatography on silicic acid columns. The identity of the purified glycosphingolipids was confirmed by mass spectrometry (18), proton NMR spectroscopy (19), and degradation studies (20,21). Gal␤3GlcNH 2 ␤3Gal␤4Glc␤1Cer (No.…”

Section: Methodsmentioning

confidence: 95%

Lactotetraosylceramide, a Novel Glycosphingolipid Receptor for Helicobacter pylori, Present in Human Gastric Epithelium

Teneberg

Leonardsson

Karlsson

et al. 2002

Journal of Biological Chemistry

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The binding of Helicobacter pylori to glycosphingolipids was examined by binding of 35 S-labeled bacteria to glycosphingolipids on thin-layer chromatograms. In addition to previously reported binding specificities, a selective binding to a non-acid tetraglycosylceramide of human meconium was found. This H. pylori binding glycosphingolipid was isolated and, on the basis of mass spectrometry, proton NMR spectroscopy, and degradation studies, were identified as Gal␤3GlcNAc␤3-Gal␤4Glc␤1Cer (lactotetraosylceramide). When using non-acid glycosphingolipid preparations from human gastric epithelial cells, an identical binding of H. pylori to the tetraglycosylceramide interval was obtained in one of seven samples. Evidence for the presence of lactotetraosylceramide in the binding-active interval was obtained by proton NMR spectroscopy of intact glycosphingolipids and by gas chromatography-electron ionization mass spectrometry of permethylated tetrasaccharides obtained by ceramide glycanase hydrolysis. The lactotetraosylceramide binding property was detected in 65 of 74 H. pylori isolates (88%). Binding of H. pylori to lactotetraosylceramide on thin-layer chromatograms was inhibited by preincubation with lactotetraose but not with lactose. Removal of the terminal galactose of lactotetraosylceramide by galactosidase hydrolysis abolished the binding as did hydrazinolysis of the acetamido group of the Nacetylglucosamine. Therefore, Gal␤3GlcNAc is an essential part of the binding epitope.Adhesion of microorganisms to target cells is regarded as a first step in pathogenesis of infections, where the specificity of the adhesins of the infectious agent on the one hand and the receptor structures expressed by the epithelial cells of the host target organ on the other are important determinants of the host range and the tissue tropism of the pathogen (1).The human gastric pathogen Helicobacter pylori is an etiologic agent of chronic active gastritis, peptic ulcer disease, and gastric adenocarcinoma (2, 3). This Gram-negative bacterium has a very distinct host range and tissue tropism, i.e. it requires human gastric epithelium for colonization (4). In the human stomach most of the bacteria are found in the mucus layer (5), but selective association of the bacteria to surface mucous cells has also been shown (4, 6).Several different binding specificities of H. pylori have previously been demonstrated. Thus, the binding of the bacterium to such diverse compounds as phosphatidylethanolamine and gangliotetraosylceramide (7), the Le b blood group determinant (8), heparan sulfate (9), the GM3 1 ganglioside and sulfatide (10, 11), and lactosylceramide (12), has been reported. A sialic aciddependent binding of H. pylori to large complex glycosphingolipids (polyglycosylceramides) has also been documented (13). However, only one H. pylori adhesin, the Le b binding BabA adhesin, has been identified to date (14).In the present study a number of different H. pylori strains were labeled with [35 S]methionine and examined for binding to a panel of...

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Section: Methodsmentioning

confidence: 95%

Lactotetraosylceramide, a Novel Glycosphingolipid Receptor for Helicobacter pylori, Present in Human Gastric Epithelium

Teneberg

Leonardsson

Karlsson

et al. 2002

Journal of Biological Chemistry

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“…Individual glycosphingolipids were isolated by repeated chromatography on silicic acid columns and by HPLC and identified by mass spectrometry (30) and 1 H NMR spectroscopy (31). Thin-layer Chromatography-Thin-layer chromatography was done on aluminum-or glass-backed silica gel 60 high performance thin-layer chromatography plates (Merck).…”

Section: Methodsmentioning

confidence: 99%

Identification of the Molecular and Genetic Basis of PX2, a Glycosphingolipid Blood Group Antigen Lacking on Globoside-deficient Erythrocytes

Westman

Benktander

Storry

et al. 2015

Journal of Biological Chemistry

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Background: Expression of x 2 glycosphingolipid (PX2) is elevated on erythrocytes from individuals with the rare P/P1/P knegative p phenotype. Results: Globoside-deficient individuals with mutated P synthase (␤1,3GalNAc-T1) lack PX2 and have anti-PX2 in plasma. Transfection of B3GALNT1 induces P and PX2 expression. Conclusion: PX2 synthesized by ␤1,3GalNAc-T1 fulfills blood group criteria. Significance: ␤1,3GalNAc-T1 uses different acceptors to form immunologically distinct glycosphingolipids.

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“…The GalNAc-Neu5Ac interaction in GM2 represents a well-defined carbohydrate-to-carbohydrate interaction. The presence of GalNAc-Neu5Ac interaction in GM2 has also been supported by the NMR studies which revealed the existence of through the space interactions between these two sugar residues [19]. To understand the catabolism of GM2, we have used a series of structurally modified GM2 to study the effect of modifications of sugar chains in this ganglioside on the GalNAcNeu5Ac interaction and the enzymatic susceptibility.…”

Section: Introductionmentioning

confidence: 87%

Effect of structural modifications of ganglioside GM2 on intra-molecular carbohydrate-to-carbohydrate interaction and enzymatic susceptibility

Kiso

et al. 2008

Biochimica et Biophysica Acta (BBA) - General Subjects

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SummaryThe effect of inter-molecular carbohydrate-to-carbohydrate interaction on basic cell biological processes has been well documented and appreciated. In contrast, very little is known about the intramolecular carbohydrate-to-carbohydrate interaction. The presence of an interaction between the GalNAc and the Neu5Ac in GM2 detected by NMR spectroscopy represents a well-defined intramolecular carbohydrate-to-carbohydrate interaction. This intriguing interaction is responsible for the GM2-epitope, GalNAcβ1Π4(Neu5Acα2Π3)Gal-, to exhibit a rigid and compact conformation. We hypothesized that this compact conformation may be the cause for both the GalNAc and the Neu5Ac in GM2 to be refractory to enzymatic hydrolysis and the GM2 activator protein is able to interact with the compact trisaccharide GM2-epitope, rendering the GalNAc and the Neu5Ac accessible to β-hexosaminidase A and sialidase. We have used a series of structurally modified GM2 to study the effect of modifications of sugar chains on the conformation and enzymatic susceptibility of this ganglioside. Our hypothesis was borne out by the fact that when the GalNAcβ1Π4Gal linkage in GM2 was converted to the GalNAcβ1Π6Gal, both the GalNAc and the Neu5Ac became susceptible to β-hexosaminidase A and sialidase, respectively, without GM2 activator protein. We hope our work will engender interest in identifying other intra-molecular carbohydrate-to-carbohydrate interactions in glycoconjugates.

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High-resolution proton NMR studies of gangliosides. 1. Use of homonuclear two-dimensional spin-echo J-correlated spectroscopy for determination of residue composition and anomeric configurations

Cited by 219 publications

References 32 publications

Lactotetraosylceramide, a Novel Glycosphingolipid Receptor for Helicobacter pylori, Present in Human Gastric Epithelium

Lactotetraosylceramide, a Novel Glycosphingolipid Receptor for Helicobacter pylori, Present in Human Gastric Epithelium

Identification of the Molecular and Genetic Basis of PX2, a Glycosphingolipid Blood Group Antigen Lacking on Globoside-deficient Erythrocytes

Effect of structural modifications of ganglioside GM2 on intra-molecular carbohydrate-to-carbohydrate interaction and enzymatic susceptibility

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