Solution conformations of GM3 ganglioside containing different sialic acid residues as revealed by NOE-based distance mapping, molecular mechanics, and molecular dynamics calculations

Siebert, Hans Christian; Reuter, Gerd; Schauer, Roland; Lieth, C.W. von der; Dąbrowski, Janusz

doi:10.1021/bi00145a014

Cited by 121 publications

(73 citation statements)

References 43 publications

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“…Comparison of our results obtained from the ab initio calculations with those from MD-simulations [11] do not show any contradictions, for example, both conformations (both angle values) of 2 100 and þ 1008 are possible according to the ab initio calculations.…”

Section: Data From Ab Initio Calculationssupporting

confidence: 57%

“…NMR-calculations and molecular dynamic (MD) simulations have successfully been carried out in order to address the question whether certain functional groups (e.g. O-acetyl groups) have a conformational influence on the carbohydrate part or are rather acting as direct contact points [6,11]. Ab initio calculations with their high degree of accuracy are applied to determine the impact of the different functional groups on the sialic acid derivatives under study.…”

Section: Introductionmentioning

confidence: 99%

“…Ab initio calculations with their high degree of accuracy are applied to determine the impact of the different functional groups on the sialic acid derivatives under study. The results obtained by this approach were correlated with MD-and NMR-data [11] and thereby used to provide further insight into the basic principles of the effect of sialic acid modifications. A combination of NMRexperiments with molecular mechanic and MD studies have proven that a remarkable structural influence of the O-acetyl and/or N-glycolyl group on the overall conformation is not detectable in the case of GM3-gangliosides [11].…”

Section: Introductionmentioning

confidence: 99%

“…The results obtained by this approach were correlated with MD-and NMR-data [11] and thereby used to provide further insight into the basic principles of the effect of sialic acid modifications. A combination of NMRexperiments with molecular mechanic and MD studies have proven that a remarkable structural influence of the O-acetyl and/or N-glycolyl group on the overall conformation is not detectable in the case of GM3-gangliosides [11]. MD-studies of higher gangliosides show that this is also the case for 9-O-acetyl-GD1a when compared to unsubstituted GD1a [6].…”

Section: Introductionmentioning

confidence: 99%

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Ab initio calculations on various sialic acids provide valuable information about sialic acid-specific enzymes

Lenthe

Boer

Havenith

et al. 2004

Journal of Molecular Structure: THEOCHEM

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This study presents ab initio calculations on six sialic acid derivatives (N-acetylneuraminic acid, 2-deoxy-2,3-didehydro-Nacetylneuraminic acid, N-acetyl-4-O-acetylneuraminic acid, N-glycolylneuraminic acid, N-glycolyl-4-O-acetylneuraminic acid and N-acetyl-9-O-acetylneuraminic acid). The calculations were carried out using the GAMESS-UK-Program. Since the charge distribution of a ligand has an essential impact on the specific interaction with an enzyme or a receptor, the precise results of ab initio calculations lead to significant information concerning possible roles of the different functional groups occurring on sialic acids. In correlation to this, valuable conclusions about the activities of different sialic acid-specific enzymes, such as sialidases, trans-sialidases, lyases and O-acetyl-or O-methyltransferases can be drawn, since these activities strongly depend on the presence or absence of the various functional groups. q 2004 Published by Elsevier B.V.

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Section: Data From Ab Initio Calculationssupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ab initio calculations on various sialic acids provide valuable information about sialic acid-specific enzymes

Lenthe

Boer

Havenith

et al. 2004

Journal of Molecular Structure: THEOCHEM

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“…2D-ROESY (Rotating Frame Overhauser Effect SpectroscopY) (22,23) and 1D-and 2D-TRNOE (TRansferred Nuclear Overhauser Effect) measurements (24-27) were used for determination of conformational parameters of the ligand in the free and in the galectin-bound state. The mixing times for ROESY and TRNOE experiments were set to 50, 100, 200 and 300 ms. NOE constraints in the free and in the bound state were evaluated using the distance mapping procedure (28)(29)(30). For the conformational analysis of the glycosidic linkage the Ramachandran-type representation was used, where distance constraints for each atom pair are expressed in the form of their , coordinates.…”

Section: Preparation Of the Ligand A Mixture Of 1-o-[3ј-(trifluoroacmentioning

confidence: 99%

NMR-Based, Molecular Dynamics- and Random Walk Molecular Mechanics-Supported Study of Conformational Aspects of a Carbohydrate Ligand (Galβ1-2Galβ1-R) for an Animal Galectin in the Free and in the Bound State

Siebert

Gilleron

Kaltner

et al. 1996

Biochemical and Biophysical Research Communications

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The binding of a carbohydrate to a lectin may affect the conformation of the ligand. To address this question for the galectin from chicken liver, the conformation of Gal␤1-2Gal␤1-R was analyzed in the free and in the galectin-bound state with 2D-ROESY-and 1D-as well as 2D-transferred NOE-experiments. A computerassisted analysis of spatial parameters of the ligand by molecular dynamics (MD) and random walk molecular mechanics (RAMM) calculations, taking different dielectric constants from ⑀ ‫ס‬ 1 to ⑀ ‫ס‬ 80 and various force fields into account, were instrumental to define the energetic minima of the free state. NMR-derived interresidual distance constraints enabled a conformational mapping. The two overlapping interresidual distance constraints obtained from transferred-NOE experiments of the galectin-ligand complex clearly support the notion that the conformation of the disaccharide in the bound state is at least very close to its global energy minimum state in solution. © 1996 Academic Press, Inc.Protein-carbohydrate interactions can guide crucial physiological reactions such as cell adhesion, inter-and intracellular glycoprotein routing and regulation of various cellular functions (1, 2). Their evident importance prompts to analyze in detail the molecular characteristics of this type of recognition in solution. The combination of computer-assisted calculations of the conformation and NMR-based experiments for the free ligand and lectin-saccharide complex provides a suitable tool to address this question. It enables us to compare spatial parameters of a certain ligand before and after association with members of a lectin family with similar binding specificity, e.g. to galactosides. Agglutinins of this class mediate cell-matrix interactions and enhance immune functions (3-5). Due to the remarkable affinity of Gal␤1-2Gal␤1-R to the immunomodulatory Viscum album agglutinin, reported previously (6, 7), we have chosen to map conformational aspects of this high-affinity ligand for galactoside-binding lectins of organisms from different branches of the evolutionary tree. Herein, we report the first study in this area for an animal galectin. Transferred nuclear Overhauser effect (TRNOE)-based experiments in combination with conformational distance mapping, random walk molecular mechanics (RAMM) and molecular dynamics (MD) calculations indicate that the actual conformations of this disaccharide in the complex and in the free form are at least very similar.

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Conformational study of asialo-GM1 (GA1) ganglioside

et al. 1997

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In order to investigate the significance of preferred conformations of the saccharide for the steric orientation and recognition of glycosphingolipids at the membrane surface, the conformational free energy calculations were carried out on the asialo‐GM1 [GA1; β‐D‐Gal(1 → 3) β‐D‐GalNAc(1 → 4) β‐D‐Gal(1 → 4) β‐D‐Glc‐O‐ceramide] using a new program CONCARB (CONformational study program for CARBohydrate) in the unhydrated and hydrated states. The overall backbone conformation of GA1 appears nearly to be extended with a little bent at the glycosidic II–III linkage, in which two pyranose rings of Gal(IV)‐GalNAc‐(III) moiety orient approximately perpendicular to those of Gal(II)‐Glc(I) moiety. This is consistent with the structures deduced from high‐sensitivity differential scanning calorimetry experiments and the nmr study on GA1. The calculated glycosidic torsion angles of the lowest free energy conformation of GA1 in the hydrated state are in accord with the structures of relevant oligosaccharides deduced from nmr experiments and hard sphere exoanomeric calculations. A comparison of the values of glycosidic torsion angles ϕ and π of GA1 and its constituent oligosaccharides indicates that the overall backbone conformation of each oligosaccharide is retained when the oligosaccharide chain becomes longer. This implies that the short‐range interactions between the nearest‐neighbored saccharides are of significant importance in stabilizing the overall backbone conformation of GA1 in both the unhydrated and hydrated states. The different orientation and hydrogen bonds of hydroxymethyl and hydroxyl groups from one oligosaccharide to another suggest that the medium‐ and long‐range interactions are also of consequence. Hydration seems to affect significantly the conformation of these groups, but not to perturb remarkably the overall backbone conformation of GA1. © 1997 John Wiley & Sons, Inc. Biopoly 42: 19–35, 1997

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Solution conformations of GM3 ganglioside containing different sialic acid residues as revealed by NOE-based distance mapping, molecular mechanics, and molecular dynamics calculations

Cited by 121 publications

References 43 publications

Ab initio calculations on various sialic acids provide valuable information about sialic acid-specific enzymes

Ab initio calculations on various sialic acids provide valuable information about sialic acid-specific enzymes

NMR-Based, Molecular Dynamics- and Random Walk Molecular Mechanics-Supported Study of Conformational Aspects of a Carbohydrate Ligand (Galβ1-2Galβ1-R) for an Animal Galectin in the Free and in the Bound State

Conformational study of asialo-GM1 (GA1) ganglioside

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