Lewis X trisaccharides normally function as essential cell-cell interaction mediators. However, oligomers of Lewis X trisaccharides expressed by the parasite Schistosoma mansoni seem to be related to its evasion of the immune response of its human host. Here we show that monoclonal antibody 54-5C10-A, which is used to diagnose schistosomiasis in humans, interacts with oligomers of at least three Lewis X trisaccharides, but not with monomeric Lewis X. We describe the sequence and the 2.5 A crystal structure of its Fab fragment and infer a possible mode of binding of the polymeric Lewis X from docking studies. Our studies indicate a radically different mode of binding compared to Fab 291-2G3-A, which is specific for monomeric Lewis X, thus providing a structural explanation of the diagnostic success of 54-5C10-A.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/prot.22356 | DOI Listing |
J Am Chem Soc
November 2024
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556-5670, United States.
Prior studies of the solution conformation of the Lewis (Le) trisaccharide, αFuc-(1→3)[βGal-(1→4)]-βGlcNAc, suggest that nonclassical inter-residue C-H···O hydrogen bonding in aqueous solution contributes to the stabilization of its 3D structure and affects its biological properties. Experimental evidence for this hydrogen bond in aqueous solution has been reported in the form of a NMR spin-coupling constant between C5'Fuc and H1″Gal measured by 2D NMR methods in unlabeled samples. A methyl glycoside of Le (MeβLe) was prepared containing selective C-labeling at C5'Fuc, and the H1″Gal signal was examined in high-field H NMR spectra for evidence of splitting or line-broadening caused by the C at C5'Fuc.
View Article and Find Full Text PDFBiochemistry
November 2024
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556-5670, United States.
An emerging NMR method, analysis, has been applied to investigate context effects on the conformational properties of several human milk oligosaccharides (HMOs). The model of the β-(1→4) linkage in the disaccharide, methyl β-lactoside (MeL), was compared to those obtained for the same linkage in the HMO trisaccharides, methyl 2'-fucosyllactoside (Me2'FL) and methyl 3-fucosyllactoside (Me3FL), and in the tetrasaccharide, methyl 2',3-difucosyllactoside (Me2',3DFL). analysis revealed significant context effects on the mean values and circular standard deviations (CSDs) of the psi (ψ) torsion angles in these linkages.
View Article and Find Full Text PDFGlycobiology
December 2024
Guangdong Engineering Technology Research Centre of Enzyme and Biocatalysis, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, No. 10 Shiliugang Road, Haizhu District, Guangzhou, Guangdong 510316, P. R. China.
Gut microbes produce α-l-fucosidases critical for utilizing human milk oligosaccharides, mucosal and dietary glycans. Although gut Parabacteroides have garnered attention for their impact on host health and disease, their CAZymes remain poorly studied. CAZome analysis of eleven gut Parabacteroides type strains revealed their capacity to degrade mucin O-glycans.
View Article and Find Full Text PDFJ Phys Chem B
September 2024
Department of Chemistry and Biochemistry and Biomolecular Sciences Institute, Florida International University, 11200 SW Eighth Street, Miami, Florida 33199, United States.
Fucosylated carbohydrate antigens play critical roles in physiology and pathology with function linked to their structural details. However, the separation and structural characterization of isomeric fucosylated epitopes remain challenging analytically. Here, we report for the first time the influence of alkali metal cations (Li, Na, K, Rb, and Cs) and halogen anions (Cl, Br, and I) on the gas-phase conformational landscapes of common fucosylated trisaccharides (Lewis A, X, and H types 1 and 2) and tetrasaccharides (Lewis B and Y) using trapped ion mobility spectrometry coupled to mass spectrometry and theoretical calculations.
View Article and Find Full Text PDFPhys Chem Chem Phys
May 2024
Department of Chemistry, Hunter College, The City University of New York, New York, NY 10065, USA.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!