AISMIG—an interactive server-side molecule image generator

Using a web browser without additional software and generating interactive high quality and high resolution images of bio-molecules is no longer a problem. Interactive visualization of 3D molecule structures by Internet browsers normally is not possible without additional software and the disadvantage of browser-based structure images (e.g. by a Java applet) is their low resolution. Scientists who want to generate 3D molecular images with high quality and high resolution (e.g. for publications or to render a molecule for a poster) therefore require separately installed software that is often not easy to use. The alternative concept is an interactive server-side rendering application that can be interfaced with any web browser. Thus it combines the advantage of the web application with the high-end rendering of a raytracer. This article addresses users who want to generate high quality images from molecular structures and do not have software installed locally for structure visualization. Often people do not have a structure viewer, such as RasMol or Chime (or even Java) installed locally but want to visualize a molecule structure interactively. AISMIG (An Interactive Server-side Molecule Image Generator) is a web service that provides a visualization of molecule structures in such cases. AISMIG-URL:

GlycoMapsDB: a database of the accessible conformational space of glycosidic linkages

Conformational energy maps of the glycosidic linkages are a valuable resource to gain information about preferred conformations and flexibility of carbohydrates. Here we present GlycoMapsDB, a new database containing more than 2500 calculated conformational maps for a variety of di- to pentasaccharide fragments contained in N- and O-glycans. Oligosaccharides representing branchpoints of N-glycans are included in the set of fragments, thus the influence of neighbouring residues is reflected in the conformational maps. During refinement of new crystal structures, maps contained in GlycoMapsDB can serve as a valuable resource to check whether the torsion values of a glycosidic linkage are located in an ‘allowed’ region similar to the Ramachandran plot analysis for proteins. This might help to improve the structural quality of the glycan data contained in the Protein Data Bank (PDB). A link between GlycoMapsDB and the PDB has been established so that the glycosidic torsions of all glycans contained in the PDB can be retrieved and compared to calculated data. The service is available at

Bioinformatics and molecular modeling in glycobiology

The field of glycobiology is concerned with the study of the structure, properties, and biological functions of the family of biomolecules called carbohydrates. Bioinformatics for glycobiology is a particularly challenging field, because carbohydrates exhibit a high structural diversity and their chains are often branched. Significant improvements in experimental analytical methods over recent years have led to a tremendous increase in the amount of carbohydrate structure data generated. Consequently, the availability of databases and tools to store, retrieve and analyze these data in an efficient way is of fundamental importance to progress in glycobiology. In this review, the various graphical representations and sequence formats of carbohydrates are introduced, and an overview of newly developed databases, the latest developments in sequence alignment and data mining, and tools to support experimental glycan analysis are presented. Finally, the field of structural glycoinformatics and molecular modeling of carbohydrates, glycoproteins, and protein–carbohydrate interaction are reviewed

Functional network of glycan-related molecules: Glyco-Net in Glycoconjugate Data Bank

<p>Abstract</p> <p>Background</p> <p>Glycans are involved in a wide range of biological process, and they play an essential role in functions such as cell differentiation, cell adhesion, pathogen-host recognition, toxin-receptor interactions, signal transduction, cancer metastasis, and immune responses. Elucidating pathways related to post-translational modifications (PTMs) such as glycosylation are of growing importance in post-genome science and technology. Graphical networks describing the relationships among glycan-related molecules, including genes, proteins, lipids and various biological events are considered extremely valuable and convenient tools for the systematic investigation of PTMs. However, there is no database which dynamically draws functional networks related to glycans.</p> <p>Description</p> <p>We have created a database called Glyco-Net <url>http://www.glycoconjugate.jp/functions/</url>, with many binary relationships among glycan-related molecules. Using search results, we can dynamically draw figures of the functional relationships among these components with nodes and arrows. A certain molecule or event corresponds to a node in the network figures, and the relationship between the molecule and the event are indicated by arrows. Since all components are treated equally, an arrow is also a node.</p> <p>Conclusions</p> <p>In this paper, we describe our new database, Glyco-Net, which is the first database to dynamically show networks of the functional profiles of glycan related molecules. The graphical networks will assist in the understanding of the role of the PTMs. In addition, since various kinds of bio-objects such as genes, proteins, and inhibitors are equally treated in Glyco-Net, we can obtain a large amount of information on the PTMs.</p

Interaction of triosephosphate isomerase from the cell surface of Staphylococcus aureus and α-(1→3)-mannooligosaccharides derived from glucuronoxylomannan of Cryptococcus neoformans

The glycolytic enzyme triosephosphate isomerase (TPI; EC 5.3.1.1) of Staphylococcus aureus is a candidate adhesion molecule for the interaction between the bacterium and the fungal pathogen Cryptococcus neoformans. TPI may recognize the mannan backbone of glucuronoxylomannan (GXM) of C. neoformans. We purified TPI from extracts of S. aureus surface proteins to investigate its binding by surface plasmon resonance analysis. The immobilized TPI reacted with GXM in a dose-dependent manner. Furthermore, the interactions between staphylococcal TPI and α-(1→3)-mannooligosaccharides derived from GXM were examined. The oligosaccharides exhibited binding with TPI; however, monomeric mannose did not. Differences in the slopes of the sensorgrams were observed between oligosaccharides with an even number of residues versus those with an odd number. A heterogeneous ligand-parallel reaction model revealed the existence of at least two binding sites on TPI. The enzymic activities of TPI were inhibited in a dose-dependent manner by α-(1→3)-mannooligosaccharides larger than triose. The binding of TPI and α-(1→3)-mannotriose near the substrate-binding site was predicted in silico (AutoDock 3.05). An oligosaccharide of size equal to or greater than triose could bind to the site, affecting enzymic activities. Moreover, affinities were indicated, especially for biose and tetraose, to another binding pocket, which would not affect enzymic activity. These data suggest a novel role for TPI, in addition to glycolysis, on the surface of S. aureus

Facettes de glycobioinformatique (applications à l'étude des interactions protéines-sucres)

Le travail décrit dans ce manuscrit rassemble les résultats obtenus au cours de ma thèse de doctorat. Ils s'inscrivent dans le domaine de la glycobioinformatique. Ils ont impliqué des développements de bases de données structurales et des applications en modélisation moléculaire des interactions protéines-sucres. Les méthodes de modélisation moléculaire ont été utilisées dans la reconstruction et dans la prédiction des structures tridimensionnelles de polysaccharides et d'oligosaccharides, ces dernières étant également établies par une approche de type haut-débit par application d'un algorithme génétique à des fins de minimisation énergétique. Les données ainsi générées ont été organisées sous la forme de bases de données relationnelles, proprement annotées (PolySca3DB et BiOligo) qui sont en libre accès pour consultation sur internet. Ces méthodes de modélisation moléculaire ont été appliquées à la caractérisation, par RMN en solution, des conformations de basse énergie d'une souche pathogène d'un polysaccharide de la bactérie E. coli. D'autres bactéries pathogènes de type gram négatif, interagissent avec des oligosaccharides par l'intermédiaire de protéines secrétées, telles que des lectines. Nous avons testé, au travers de l'utilisation de méthodes d'amarrage moléculaire, la possibilité d'identifier de manière automatique, la nature de ces interactions, en prenant comme cibles des épitopes oligosaccharidiques fucosylés. Les résultats de ces recherches ont été comparés, de manière critique, à ceux issus de l'application de bio-puces à sucres et de calorimétrie isotherme de titration. Les conclusions et perspectives de ces travaux sont présentées dans un article de revue consacré à l'application des méthodes de chimie computationnelle dans l'étude des interactions protéines-glucides qui viennent compléter l'arsenal des outils dédiés au champs de recherche couvert par la glycobiologie structurale et moléculaire.This thesis presents an account of two important facets of glycobioinformatics, comprising database development and molecular modeling of 3D structures of carbohydrates alongside the simulation of protein-carbohydrate interactions. Classical molecular modeling techniques were used to reconstruct 3D polysaccharide structures from experimentally determined atomic coordinates, or known starting points about their structures were used as guidelines to model them. A genetic algorithm search was employed as a high-throughput technique to characterize low energy conformers of bioactive oligosaccharides. The data generated were organized into two open-access relational databases, namely, PolySac3DB and BiOligo, for use by the scientific community. The validation of the molecular techniques used were performed using solution phase NMR experiments on four entero aggregative pathogenic E. coli strains, and were found to be robust and realistic. Further, the impact of the presentation of human fucosylated oligosaccharide epitopes to lectins from opportunistic gram negative bacteria, was investigated in a screening study using molecular docking studies, which could help in evaluating the feasibility of using automated docking procedures in such instances as well as deciphering binding data from glycan array experiments and also correlated to isothermal calorimetry data. On comparison with high-resolution experimental crystal complexes, automated docking was found to delineate the present level of applicability, while emphasizing the need of constant monitoring and possible filtering of the results obtained. Finally, a review of the present status of the computational aspects of protein-carbohydrate interaction studies is discussed in the perspectives of using molecular modeling and simulation studies to probe this aspect of molecular and structural glycobiology.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

Comparison of glycoside hydrolase family 3 β-xylosidases from basidiomycetes and ascomycetes reveals evolutionarily distinct xylan degradation systems

Xylan is the most common hemicellulose in plant cell walls, though the structure of xylan polymers differs between plant species. Here, to gain a better understanding of fungal xylan degradation systems, which can enhance enzymatic saccharification of plant cell walls in industrial processes, we conducted a comparative study of two glycoside hydrolase family 3 (GH3) β-xylosidases (Bxls), one from the basidiomycete Phanerochaete chrysosporium (PcBxl3), and the other from the ascomycete Trichoderma reesei (TrXyl3A). A comparison of the crystal structures of the two enzymes, both with saccharide bound at the catalytic center, provided insight into the basis of substrate binding at each subsite. PcBxl3 has a substrate-binding pocket at subsite -1, while TrXyl3A has an extra loop that contains additional binding subsites. Furthermore, kinetic experiments revealed that PcBxl3 degraded xylooligosaccharides faster than TrXyl3A, while the KM values of TrXyl3A were lower than those of PcBxl3. The relationship between substrate specificity and degree of polymerization of substrates suggested that PcBxl3 preferentially degrades xylobiose (X2), while TrXyl3A degrades longer xylooligosaccharides. Moreover, docking simulation supported the existence of extended positive subsites of TrXyl3A in the extra loop located at the N-terminus of the protein. Finally, phylogenetic analysis suggests that wood-decaying basidiomycetes use Bxls such as PcBxl3 that act efficiently on xylan structures from woody plants, whereas molds use instead Bxls that efficiently degrade xylan from grass. Our results provide added insights into fungal efficient xylan degradation systems

Structural Characterization of the Extracellular Domain of CASPR2 and Insights into Its Association with the Novel Ligand Contactin1

Contactin-associated protein-like 2 (CNTNAP2) encodes for CASPR2, a multidomain single transmembrane protein belonging to the neurexin superfamily that has been implicated in a broad range of human phenotypes including autism and language impairment. Using a combination of biophysical techniques, including small angle x-ray scattering, single particle electron microscopy, analytical ultracentrifugation, and bio-layer interferometry, we present novel structural and functional data that relate the architecture of the extracellular domain of CASPR2 to a previously unknown ligand, Contactin1 (CNTN1). Structurally, CASPR2 is highly glycosylated and has an overall compact architecture. Functionally, we show that CASPR2 associates with micromolar affinity with CNTN1 but, under the same conditions, it does not interact with any of the other members of the contactin family. Moreover, by using dissociated hippocampal neurons we show that microbeads loaded with CASPR2, but not with a deletion mutant, co-localize with transfected CNTN1, suggesting that CNTN1 is an endogenous ligand for CASPR2. These data provide novel insights into the structure and function of CASPR2, suggesting a complex role of CASPR2 in the nervous system

Polypeptide N-acetylgalactosamine transferase 3: a post-translational writer on human health

Polypeptide N-acetylgalactosamine transferase 3 (ppGalNAc-T3) is an enzyme involved in the initiation of O-GalNAc glycan biosynthesis. Acting as a writer of frequent post-translational modification (PTM) on human proteins, ppGalNAc-T3 has key functions in the homeostasis of human cells and tissues. We review the relevant roles of this molecule in the biosynthesis of O-GalNAc glycans, as well as in biological functions related to human physiological and pathological conditions. With main emphasis in ppGalNAc-T3, we draw attention to the different ways involved in the modulation of ppGalNAc-Ts enzymatic activity. In addition, we take notice on recent reports of ppGalNAc-T3 having different subcellular localizations, highlight critical intrinsic and extrinsic functions in cellular physiology that are exerted by ppGalNAc-T3-synthesized PTMs, and provide an update on several human pathologies associated with dysfunctional ppGalNAc-T3. Finally, we propose biotechnological tools as new therapeutic options for the treatment of pathologies related to altered ppGalNAc-T3. KEY MESSAGES: ppGalNAc-T3 is a key enzyme in the human O-GalNAc glycans biosynthesis. enzyme activity is regulated by PTMs, lectin domain and protein-protein interactions. ppGalNAc-T3 is located in human Golgi apparatus and cell nucleus. ppGalNAc-T3 has a central role in cell physiology as well as in several pathologies. Biotechnological tools for pathological management are proposed.Fil: Garay, Yohana Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Cejas, Romina Beatríz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Lorenz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; ArgentinaFil: Zlocowski, Natacha. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Parodi, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Ferrero, Franco Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Angeloni, Genaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Alfonso García, Valentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Sendra, Victor German. Tufts University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lardone, Ricardo Dante. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Irazoqui, Fernando Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentin