| 1. |
- Bonnardel, Francois, et al.
(författare)
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Architecture and Evolution of Blade Assembly in beta-propeller Lectins
- 2019
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Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 27:5, s. 764-
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Tidskriftsartikel (refereegranskat)abstract
- Lectins with a beta-propeller fold bind glycans on the cell surface through multivalent binding sites and appropriate directionality. These proteins are formed by repeats of short domains, raising questions about evolutionary duplication. However, these repeats are difficult to detect in translated genomes and seldom correctly annotated in sequence databases. To address these issues, we defined the blade signature of the five types of beta-propellers using 3D-structural data. With these templates, we predicted 3,887 beta-propeller lectins in 1,889 species and organized this information in a searchable online database. The data reveal a widespread distribution of beta-propeller lectins across species. Prediction also emphasizes multiple architectures and led to the discovery of a beta-propeller assembly scenario. This was confirmed by producing and characterizing a predicted protein coded in the genome of Kordia zhangzhouensis. The crystal structure uncovers an intermediate in the evolution of beta-propeller assembly and demonstrates the power of our tools.
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| 2. |
- Mohammad, Rizgar Hassan, et al.
(författare)
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Isolation and characterisation of 13 pterosins and pterosides from bracken (Pteridium aquilinum (L.) Kuhn) rhizome
- 2016
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Ingår i: Phytochemistry. - : Elsevier BV. - 0031-9422 .- 1873-3700. ; 128, s. 82-94
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Tidskriftsartikel (refereegranskat)abstract
- Systematic phytochemical investigations of the underground rhizome of Pteridium aquilinum (L.) Kuhn (Dennstaedtiaceae) afforded thirty-five pterosins and pterosides. By detailed analysis of one- and two-dimensional nuclear magnetic resonance spectroscopy, circular dichroism (CD) and high-resolution mass spectrometric data, thirteen previously undescribed pterosins and pterosides have been identified. Interestingly, for the first time 12-O-beta-D-glucopyranoside substituted pterosins, rhedynosides C and D, and the sulfate-containing pterosin, rhedynosin H, alongside the two known compounds, histiopterosin A and (2S)-pteroside A2, were isolated from the rhizomes of subsp. aquilinum of bracken. In addition, six-membered cyclic ether pterosins and pterosides, rhedynosin A and rhedynoside A, are the first examples of this type of pterosin-sesquiterpenoid. Additionally, the three previously reported compounds (rhedynosin I, (2S)-2-hydroxymethylpterosin E and (2S)-12-hydroxypterosin A) were obtained for the first time from plants as opposed to mammalian metabolic products. Single crystal X-ray diffraction analysis was applied to the previously undescribed compounds (2R)-rhedynoside B, (2R)pteroside B and (2S)-pteroside K, yielding the first crystal structures for pterosides, and three known pterosins, (2S)-pterosin A, trans-pterosin C and cis-pterosin C. Rhedynosin C is the only example of the cyclic lactone pterosins with a keto group at position C-14. Six selected pterosins ((2S)-pterosin A, (2R)pterosin B and trans-pterosin C) and associated glycosides ((2S)-pteroside A, (2R)-pteroside B and pterbside Z) were assessed for their anti -diabetic activity using an intestinal glucose uptake assay; all were found to be inactive at 300 mu M.
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| 3. |
- Moonens, Kristof, et al.
(författare)
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Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori
- 2016
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Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 19:1, s. 55-66
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Tidskriftsartikel (refereegranskat)abstract
- The Helicobacter pylori adhesin BabA binds mucosal ABO/Le b blood group (bg) carbohydrates. BabA facilitates bacterial attachment to gastric surfaces, increasing strain virulence and forming a recognized risk factor for peptic ulcers and gastric cancer. High sequence variation causes BabA functional diversity, but the underlying structural-molecular determinants are unknown. We generated X-ray structures of representative BabA isoforms that reveal a polymorphic, three-pronged Le(b) binding site. Two diversity loops, DL1 and DL2, provide adaptive control to binding affinity, notably ABO versus O bg preference. H. pylori strains can switch bg preference with single DL1 amino acid substitutions, and can coexpress functionally divergent BabA isoforms. The anchor point for receptor binding is the embrace of an ABO fucose residue by a disulfide-clasped loop, which is inactivated by reduction. Treatment with the redox-active pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in H. pylori-infected Le(b)-expressing mice, providing perspectives on possible H. pylori eradication therapies.
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| 4. |
- Ramos-Morales, Eva, et al.
(författare)
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Antiprotozoal Effect of Saponins in the Rumen Can Be Enhanced by Chemical Modifications in Their Structure
- 2017
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The antiprotozoal effect of saponins is transitory, as when saponins are deglycosylated to the sapogenin by rumen microorganisms they become inactive. We postulated that the substitution of the sugar moiety of the saponin with small polar residues would produce sapogen-like analogs which might be resistant to degradation in the rumen as they would not be enzymatically cleaved, allowing the antiprotozoal effect to persist over time. In this study, we used an acute assay based on the ability of protozoa to break down [14C] leucine-labeled Streptococcus bovis and a longer term assay based on protozoal motility over 24 h to evaluate both the antiprotozoal effect and the stability of this effect with fifteen hederagenin bis-esters esterified with two identical groups, and five cholesterol and cholic acid based derivatives carrying one to three succinate residues. The acute antiprotozoal effect of hederagenin derivatives was more pronounced than that of cholesterol and cholic acid derivatives. Modifications in the structure of hederagenin, cholesterol, and cholic acid derivatives resulted in compounds with different biological activities in terms of acute effect and stability, although those which were highly toxic to protozoa were not always the most stable over time. Most of the hederagenin bis-esters, and in particular hederagenin bis-succinate (TSB24), hederagenin bis-betainate dichloride (TSB37) and hederagenin bis-adipate (TSB47) had a persistent effect against rumen protozoa in vitro, shifting the fermentation pattern toward higher propionate and lower butyrate. These chemically modified triterpenes could potentially be used in ruminant diets as an effective defaunation agent to, ultimately, increase nitrogen utilization, decrease methane emissions, and enhance animal production. Further trials in vivo or in long term rumen simulators are now needed to confirm the in vitro observations presented.
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| 5. |
- Ramos-Morales, Eva, et al.
(författare)
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Improving the antiprotozoal effect of saponins in the rumen by combination with glycosidase inhibiting iminosugars or by modification of their chemical structure
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- The antiprotozoal effect of saponins is transitory, as when saponins are deglycosylated to sapogenins by rumen microorganisms they become inactive. We hypothesised that the combination of saponins with glycosidase-inhibiting iminosugars might potentially increase the effectiveness of saponins over time by preventing their deglycosylation in the rumen. Alternatively, modifying the structure of the saponins by substituting the sugar moiety with other small polar residues might maintain their activity as the sugar substitute would not be enzymatically cleaved. The aim of this in vitro study was to evaluate the acute antiprotozoal effect and the stability of this effect over a 24 h incubation period using ivy saponins, a stevia extract rich in iminosugars, ivy saponins with stevia extract, and a chemically modified ivy saponin, hederagenin bis-succinate (HBS). The effects on fermentation parameters and rumen bacterial communities were also studied. Ivy saponins with stevia and HBS had a greater antiprotozoal effect than ivy saponins, and this effect was maintained after 24 h of incubation (P<0.001). The combination of ivy and stevia extracts was more effective in shifting the fermentation pattern towards higher propionate (+39%) and lower butyrate (-32%) and lower ammonia concentration (-64%) than the extracts incubated separately. HBS caused a decrease in butyrate (-45%) and an increase in propionate (+43%) molar proportions. However, the decrease in ammonia concentration (-42%) observed in the presence of HBS was less than that caused by ivy saponins, either alone or with stevia. Whereas HBS and stevia impacted on bacterial population in terms of community structure, only HBS had an effect in terms of biodiversity (P<0.05). It was concluded that ivy saponins with stevia and the modified saponin HBS had a strong antiprotozoal effect, although they differed in their effects on fermentation parameters and bacteria communities. Ivy saponins combined with an iminosugar-rich stevia extract and/or HBS should be evaluated to determine their antiprotozoal effect in vivo.
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| 6. |
- Vetro, Maria, et al.
(författare)
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Preparation and immunogenicity of gold glyco-nanoparticles as antipneumococcal vaccine model
- 2017
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Ingår i: Nanomedicine. - : Future Medicine Ltd. - 1743-5889 .- 1748-6963. ; 12:1, s. 13-23
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Nanotechnology-based fully synthetic carbohydrate vaccines are promising alternatives to classic polysaccharide/protein conjugate vaccines. We have prepared gold glyco-nanoparticles (GNP) bearing two synthetic carbohydrate antigens related to serotypes 19F and 14 of Streptococcus pneumoniae and evaluated their immunogenicity in vivo. Results: A tetrasaccharide fragment of serotype 14 (Tetra-14), a trisaccharide fragment of serotype 19F (Tri-19F), a T-helper peptide and D-glucose were loaded onto GNP in different ratios. Mice immunization showed that the concomitant presence of Tri-19F and Tetra-14 on the same nanoparticle critically enhanced the titers of specific IgG antibodies toward type 14 polysaccharide compared with GNP exclusively displaying Tetra-14, while no IgG antibodies against type 19F polysaccharide were elicited. Conclusion: This work is a step forward toward synthetic nanosystems combining carbohydrate antigens and immunogenic peptides as potential carbohydrate-based vaccines.
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