Limitations in the description of conformational preferences of C-disaccharides: The (1 → 3)-C-mannobiose case

Raich, Ivan; Lövyova, Zuzana; Trnka, Ladislav; Parkan, Kamil; Kessler, Jiří; Pohl, Radek; Kaminský, Jakub

doi:10.1016/j.carres.2017.09.006

“…To study the glycosidic linkages, we simulated the Raman and ROA spectra of four disaccharides (trehalose and three methyl mannobioses(1→2, 1→3, and 1→6 linked)) using ensemble generated either by unbiased MD simulations, or by advanced sampling techniques. Just briefly, simulations of M12 and M13 provided similar conformational profiles with the global minimum at { ϕ 1 , ϕ 2 } of (-45, 35) or (-45, 22), respectively, which agrees with previous studies [ 45 , 59 , 60 ]. On the contrary, the simulation of M16 reveals that the global minimum is the extended structure with { ϕ 1 , ϕ 2 } of (180, 180).…”

Section: Discussionsupporting

confidence: 89%

“…The 1!6 linked disaccharide is a rather special case as it possesses an additional degree of freedom. Note that conformational preferences of differently linked mannobioses have been studied previously under various conditions and using different methods for saccharides in their free states or as bound to lectins [44][45][46][47][48]. Similarly, also trehalose have been thoroughly studied predominantly using NMR and/or MD simulations [49][50][51].…”

Section: Conformation Along the Glycosidic Bondsmentioning

confidence: 99%

Use of Raman and Raman optical activity to extract atomistic details of saccharides in aqueous solution

Palivec

¹

,

Johannessen

²

,

Kaminský

³

et al. 2022

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Sugars are crucial components in biosystems and industrial applications. In aqueous environments, the natural state of short saccharides or charged glycosaminoglycans is floating and wiggling in solution. Therefore, tools to characterize their structure in a native aqueous environment are crucial but not always available. Here, we show that a combination of Raman/ROA and, on occasions, NMR experiments with Molecular Dynamics (MD) and Quantum Mechanics (QM) is a viable method to gain insights into structural features of sugars in solutions. Combining these methods provides information about accessible ring puckering conformers and their proportions. It also provides information about the conformation of the linkage between the sugar monomers, i.e., glycosidic bonds, allowing for identifying significantly accessible conformers and their relative abundance. For mixtures of sugar moieties, this method enables the deconvolution of the Raman/ROA spectra to find the actual amounts of its molecular constituents, serving as an effective analytical technique. For example, it allows calculating anomeric ratios for reducing sugars and analyzing more complex sugar mixtures to elucidate their real content. Altogether, we show that combining Raman/ROA spectroscopies with simulations is a versatile method applicable to saccharides. It allows for accessing many features with precision comparable to other methods routinely used for this task, making it a viable alternative. Furthermore, we prove that the proposed technique can scale up by studying the complicated Raffinose trisaccharide, and therefore, we expect its wide adoption to characterize sugar structural features in solution.

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“…Just briefly, simulations of M12 and M13 provided similar conformational profiles with the global minimum at { ϕ 1 , ϕ 2 } of (−45, 35) or (−45, 22), respectively, which agrees with previous studies. 40,54,55 On the contrary, the simulation of M16 reveals that the global minimum is the extended structure with { ϕ 1 , ϕ 2 } of (180, 180). All but the 1→6 mannobiose provide a good agreement with experimental spectra when using unbiased MD ensemble.…”

Section: Discussionmentioning

confidence: 97%

“…Note that conformational preferences of differently linked mannobioses have been studied previously under various conditions and using different methods for saccharides in their free states or as bound to lectins. [39][40][41][42][43] Similarly, also trehalose have been thoroughly studied predominantly using NMR and/or MD simulations. 44-46…”

Section: Conformation Along the Glycosidic Bondsmentioning

confidence: 99%

Use of Raman and Raman optical activity to extract atomistic details of saccharides in aqueous solution

Palivec

¹

,

Johannessen

²

,

Kaminský

³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Sugars are crucial components in biosystems and industrial applications. In aqueous environments, the natural state of short saccharides or charged glycosaminoglycans is floating and wiggling in solution. Therefore, tools to characterize their structure in a native aqueous environment are crucial but not always available. Here, we show that a combination of Raman/ROA and, on occasions, NMR experiments with Molecular Dynamics (MD) and Quantum Mechanics (QM) is a viable method to gain insights into structural features of sugars in solutions. Combining these methods provides information about accessible ring puckering conformers and their proportions. It also provides information about the conformation of the linkage between the sugar monomers, i.e., glycosidic bonds, allowing for identifying significantly accessible conformers and their relative abundance. For mixtures of sugar moieties, this method enables the deconvolution of the Raman/ROA spectra to find the actual amounts of its molecular constituents, serving as an effective analytical technique. For example, it allows calculating anomeric ratios for reducing sugars and analyzing more complex sugar mixtures to elucidate their real content. Altogether, we show that combining Raman/ROA spectroscopies with simulations is a versatile method applicable to saccharides. It allows for accessing many features with precision comparable to other methods routinely used for this task, making it a viable alternative. Furthermore, we prove that the proposed technique can scale up by studying the complicated Raffinose trisaccharide, and therefore, we expect its wide adoption to characterize sugar structural features in solution.

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“…However, two recent works in organic chemistry and biochemistry inspired a strategy to demonstrate distortion of α-1,2-mannobiose 1 when forming a Michaelis complex with GH92 enzymes. [23][24][25] On the one hand, the synthesis and conformational analysis of Coligosaccharides 22,23 provided an evidence of a group of molecules capable to mimic natural carbohydrates. On the other hand, Li et al were capable to characterize and crystallize a Ca 2+ -dependent α-1,2-mannosidase from Enterococcus faecalis (EfGH92), which has two domains like other GH92 mannosidases.…”

mentioning

confidence: 99%

Unlocking the hydrolytic mechanism of GH92 α-1,2-mannosidases: computation inspires using C-glycosides as Michaelis complex mimics

Alonso-Gil

¹

,

Parkan

²

,

Kaminský

³

et al. 2021

Preprint

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0

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The conformational changes in a sugar moiety along the hydrolytic pathway are key to understand the mechanism of glycoside hydrolases (GHs) and to design new inhibitors. The two predominant itineraries for mannosidases go via OS2  B2,5  1S5 and 3S  3H4  1C4. For the CAZy family 92, the conformational itinerary was unknown. Published complexes of Bacteroides thetaiotaomicron GH92 catalyst with a S-glycoside and mannoimidazole indicate a 4C1  4H5/1S5  1S5 mechanism. However, as observed with the GH125 family, S-glycosides may not act always as good mimics of GH’s natural substrate. Here we present a cooperative study between computations and experiments where our results predict the E5  B2,5/1S5  1S5 pathway for GH92 enzymes. Furthermore, we demonstrate the Michaelis complex mimicry of a new kind of C-disaccharides, whose biochemical applicability was still a chimera.

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Limitations in the description of conformational preferences of C-disaccharides: The (1 → 3)-C-mannobiose case

Cited by 9 publications

References 70 publications

Use of Raman and Raman optical activity to extract atomistic details of saccharides in aqueous solution

Use of Raman and Raman optical activity to extract atomistic details of saccharides in aqueous solution

Use of Raman and Raman optical activity to extract atomistic details of saccharides in aqueous solution

Unlocking the hydrolytic mechanism of GH92 α-1,2-mannosidases: computation inspires using C-glycosides as Michaelis complex mimics

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