Structure, conformation, and dynamics of bioactive oligosaccharides: theoretical approaches and experimental validations

The crystal structure of the 1:1 complex of β-cyclodextrin with trans-cinnamic acid

Elucidation of the intra- and intermolecular carbohydrate-protein interactions would greatly contribute toward obtaining a better understanding of the structure-function correlations of the protein-linked glycans. The weak interactions involving C-H...O have recently been attracting immense attention in the domain of biomolecular recognition. However, there has been no report so far on the occurrence of C-H...O hydrogen bonds in the crystal structures of models and analogs of N-glycoproteins. We present herein an analysis of C-H...O interactions in the crystal structures of all N-glycoprotein linkage region models and analogs. The study reveals a cooperative network of bifurcated hydrogen bonds consisting of N-H...O and C-H...O interactions seen uniquely for the models. The cooperative network consists of two antiparallel chains of bifurcated hydrogen bonds, one involving N1-H, C2'-H and O1' of the aglycon moiety and the other involving N2-H, C1-H and O1'' of the sugar. Such bifurcated hydrogen bonds between the core glycan and protein are likely to play an important role in the folding and stabilization of proteins.

/pdf/observation-of-a-unique-pattern-of-bifurcated-hydrogen-bonds-3a95hzbv0l.pdf

Observation of a unique pattern of bifurcated hydrogen bonds in the crystal structures of the N-glycoprotein linkage region models.

There is an increasing interest in clarifying the role of bN-acetyl-d-glucosamine (b-GlcNAc) since the discovery that it modifies the chemical, biochemical, and biomedical behavior of an increasing number of cytoplasmic and nuclear proteins, such as transcription factors, nuclear pore proteins, oncogene products, tumor suppressors, and cytoskeletal proteins. This post-translational glycosylation is highly dynamic and draws comparisons with protein phosphorylation as a biological control mechanism. It has been implicated in gene transcription, nuclear trafficking, protein translation, signal transduction, regulation of protein–protein interactions, and the sensing of nutritional levels within the cell. Furthermore, there is clear evidence that the aberrant OGlcNAc modification of proteins is correlated with diabetes, tumorgenesis, and even with Alzheimer s disease. From a structural point of view, O-GlcNAc glycosylation sites do not show obvious consensus sequences. Additionally, in contrast to classical protein glycosylation, O-GlcNAc is not elongated or further modified with a complex array of glycans. However, in spite of the importance of O-GlcNAc glycosylation, sparse information has been reported to date concerning the geometry and dynamics of b-O-GlcNAc-Ser and b-O-GlcNAc-Thr motifs. On the contrary, significant progress has been made with regard to the understanding of the structural properties of the b-N-GlcNAc-Asn fragment. In fact, while numerous crystal structures containing this fragment have been reported to date, only one crystal structure with a serine residue glycosylated with a b-O-GlcNAc has been deposited in the Protein Data Bank. This crystal structure shows the complex between a b-O-GlcNAc glycopeptide with the sequence FAPSNYPAL (named K3G) and the MHC Class 1 H-2D antibody. The authors suggested the occurrence of two conformations for the O-GlcNAc-Ser glycosidic linkage, each displaying similar occupancy. This experimental finding clearly suggests a significant degree of mobility for this moiety. One of these conformers is shown in Figure 1. On the other hand, the conformational study in aqueous solution of glycopeptides containing the b-O-GlcNAc-Ser/

/pdf/insights-into-the-geometrical-features-underlying-b-o-glcnac-3tg3v8l1yi.pdf

Insights into the Geometrical Features Underlying β-O-GlcNAc Glycosylation: Water Pockets Drastically Modulate the Interactions between the Carbohydrate and the Peptide Backbone

On the structural significance of the linkage region constituents of N-glycoproteins: an X-ray crystallographic investigation using models and analogs.

Subramanyam Srinivasan

Papers

Crystal structure of a hydrated N-glycoprotein linkage region model and its analogue: Hydrogen bonding and π–π stacking driven molecular assembly