Comparative analysis of ganglioside conformations by MD simulations: implications for specific recognition by proteins

Vasudevan, Sheeja V.; Balaji, Petety V.

doi:10.1016/s0166-1280(01)00813-2

Cited by 15 publications

(7 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Water mediated hydrogen bonding interaction plays a dominant role in stabilizing the conformational structures of these neuraminic acid derivatives. The accessible conformations for neuraminic acid analogues with multiple substituents holding side chain linkages observed by the present MD study correlate well with those reported for similar linkages in various Neu5Ac-α2→8-Neu5Ac moiety present in all the di- and tri-sialogangliosides by earlier studies[1112]. Present MD results show a dynamic behaviour for χ 1 of analogue 10 (5-N-acetyl-9-amino-9-deoxy neuraminic acid) at the cost of 10 kcal/mol (Fig.…”

Section: Discussionsupporting

confidence: 90%

Molecular dynamics of sialic acid analogues and their interaction with influenza hemagglutinin

Blessia

Rapheal²

2010

Indian J Pharm Sci

View full text Add to dashboard Cite

Synthetic sialic acid analogues with multiple modifications at different positions(C-1/C-2/C-4/C-8/C-9) are investigated by molecular mechanics and molecular dynamics to determine their conformational preferences and structural stability to interact with their natural receptors. Sialic acids with multiple modifications are soaked in a periodic box of water as solvent. Molecular mechanics and a 2 nanosecond molecular dynamics are done using amber force fields with 30 picosecond equilibrium. Direct and water mediated hydrogen bonds existing in the sialic acid analogues, aiding for their structural stabilization are identified in this study. The accessible conformations of side chain linkages of sialic acid analogues holding multiple substituents are determined from molecular dynamics trajectory at every 1ps interval. Transitions between different minimum energy regions in conformational maps are also noticed in C-1, C-2, C-4, C-8 and C-9 substituents. Docking studies were done to find the binding mode of the sialic acid analogues with Influenza hemagglutinin. This finding provides stereo chemical explanation and conformational preference of sialic acid analogues which may be crucial for the design of sialic acid analogues as inhibitors for different sialic acid specific pathogenic proteins such as influenza toxins and neuraminidases.

show abstract

Section: Discussionsupporting

confidence: 90%

Molecular dynamics of sialic acid analogues and their interaction with influenza hemagglutinin

Blessia

Rapheal²

2010

Indian J Pharm Sci

View full text Add to dashboard Cite

show abstract

“…The ␣(2, (Table 3) demonstrates that there is a large rotational difference about the O 2 -C8Ј bond (where Ј represents an atom belonging to the underlying sugar). This is supported by molecular dynamics simulations (37,38,43), which indicate that all three staggered conformations are accessible for . Additionally, and angles diverge significantly between ligands, demonstrating a large freedom about the O 2 -C7Ј and C7Ј-C8Ј bonds.…”

Section: Resultsmentioning

confidence: 60%

“…The conformation of the primary sialic acid allows hydrogen bonding between the C8 The Crystal Structure of Siglec-7 Complexed with GT1b hydroxyl and the C1 carboxyl group. Such a conformation has been accessed in molecular dynamics simulations (37,38). Four intramolecular hydrogen bonds are possible with the branch point Gal, two with Neu5Ac2, and two with Glc.…”

Section: Resultsmentioning

confidence: 99%

Siglec-7 Undergoes a Major Conformational Change When Complexed with the α(2,8)-Disialylganglioside GT1b

Attrill

Imamura

Sharma

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

The siglecs are a group of mammalian sialic acid binding receptors expressed predominantly in the immune system. The CD33-related siglecs show complex recognition patterns for sialylated glycans. Siglec-7 shows a preference for ␣(2,8)-disialylated ligands and provides a structural template for studying the key interactions that drive this selectivity. We have co-crystallized Siglec-7 with a synthetic oligosaccharide corresponding to the ␣(2,8)-disialylated ganglioside GT1b. The crystal structure of the complex offers a first glimpse into how this important family of lectins binds the structurally diverse gangliosides. The structure reveals that the C-C loop, a region implicated in previous studies as driving siglec specificity, undergoes a dramatic conformational shift, allowing it to interact with the underlying neutral glycan core of the ganglioside. The structural data in combination with mutagenesis studies show that binding of the ganglioside is driven by extensive hydrophobic contacts together with key polar interactions and that the binding site structure is complementary to preferred solution conformations of GT1b.

show abstract

“…However, the generation of malondialdehyde as a breakdown product of lipid peroxide decompensation was significantly decreased (P,0.01) in the presence of the disialoganglioside GD1b and the trisialoganglioside GT1b. 17 This could be explained by the specific position of sialic acid residues in the gangliosides of the b-ganglioseries (two sialic acids linked to the inner galactose) [27][28][29] and their ability to chelate ferrous ions and inhibit the propagation of the lipid peroxidative chain reaction and malondialdehyde production.…”

Section: Gangliosides and Spermatozoamentioning

confidence: 99%

“…26 Depending on the number of sialic acid residues on the inner galactose, gangliosides belong to either b-ganglio-series (GD1b and GT1b) or a-ganglio-series (GM1 and GD1a). 27 Studies of their molecular structures have shown that the number of sugar units and the position and linkage type of sialic acids distinguish each ganglioside 28 and affect their physicochemical properties. 29 Thus, the disialoganglioside GD1b has two sialic acids linked to the inner galactose, whereas GD1a has one sialic acid on the inner galactose and another on the terminal galactose.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

Gavella¹,

Lipovac²

2013

Asian J Androl

View full text Add to dashboard Cite

This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species (ROS)-mediated damage. The antioxidative efficacy of exogenous gangliosides in protecting different cells encouraged us to examine their ability to protect human spermatozoa. Gangliosides are sialic acid-containing glycosphingolipids with strong amphiphilic character due to the bulky headgroup made of several sugar rings with sialic acid residues and the double-tailed hydrophobic lipid moiety. The amphiphilicity of gangliosides allows them to exist as micelles in aqueous media when they are present at a concentration above their critical micellar concentration. The protective effect of ganglioside micelles on spermatozoa is believed to stem from their ability to scavenge free radicals and prevent their damaging effects. In our study, we particularly focused our attention on the protective effect of ganglioside micelles on DNA in human spermatozoa exposed to cryopreservation. The results indicate that ganglioside micelles can modulate the hydrophobic properties of the sperm membrane to increase tolerance to DNA fragmentation, thus protecting the DNA from cryopreservation-induced damage. Further actions of ganglioside micelles, which were documented by biochemical and biophysical studies, included (i) the modulation of superoxide anion generation by increasing the diffusion barrier for membrane events responsible for signal translocation to the interior of the cell; (ii) the inhibition of iron-catalysed hydroxyl radical formation due to the iron chelation potential of gangliosides; and (iii) inhibition of hydrogen peroxide diffusion across the sperm membrane.

show abstract

Comparative analysis of ganglioside conformations by MD simulations: implications for specific recognition by proteins

Cited by 15 publications

References 79 publications

Molecular dynamics of sialic acid analogues and their interaction with influenza hemagglutinin

Molecular dynamics of sialic acid analogues and their interaction with influenza hemagglutinin

Siglec-7 Undergoes a Major Conformational Change When Complexed with the α(2,8)-Disialylganglioside GT1b

Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

Contact Info

Product

Resources

About