Showing papers by "Serge Pérez published in 2020"

GAG-DB, the New Interface of the Three-Dimensional Landscape of Glycosaminoglycans.

Abstract: Glycosaminoglycans (GAGs) are complex linear polysaccharides. GAG-DB is a curated database that classifies the three-dimensional features of the six mammalian GAGs (chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, hyaluronan, and keratan sulfate) and their oligosaccharides complexed with proteins. The entries are structures of GAG and GAG-protein complexes determined by X-ray single-crystal diffraction methods, X-ray fiber diffractometry, solution NMR spectroscopy, and scattering data often associated with molecular modeling. We designed the database architecture and the navigation tools to query the database with the Protein Data Bank (PDB), UniProtKB, and GlyTouCan (universal glycan repository) identifiers. Special attention was devoted to the description of the bound glycan ligands using simple graphical representation and numerical format for cross-referencing to other databases in glycoscience and functional data. GAG-DB provides detailed information on GAGs, their bound protein ligands, and features their interactions using several open access applications. Binding covers interactions between monosaccharides and protein monosaccharide units and the evaluation of quaternary structure. GAG-DB is freely available.

The architecture of starch blocklets follows phyllotaxic rules.

Abstract: The starch granule is Nature's way to store energy in green plants over long periods. Irrespective of their origins, starches display distinct structural features that are the fingerprints of levels of organization over six orders of magnitude. We hypothesized that Nature retains hierarchical material structures at all levels and that some general rules control the morphogenesis of these structures. We considered the occurrence of a «phyllotaxis» like features that would develop at scales ranging from nano to micrometres, and developed a novel geometric model capable of building complex structures from simple components. We applied it, according to the Fibonacci Golden Angle, to form several Golden Spirals, and derived theoretical models to simulate scattering patterns. A GSE, constructed with elements made up of parallel stranded double-helices, displayed shapes, sizes and high compactness reminiscent of the most intriguing structural element: the 'blocklet'. From the convergence between the experimental findings and the theoretical construction, we suggest that the «phyllotactic» model represents an amylopectin macromolecule, with a high molecular weight. Our results offer a new vision to some previous models of starch. They complete a consistent description of the levels of organization over four orders of magnitude of the starch granule.

Structural Database for Lectins and the UniLectin Web Platform.

Abstract: The search for new biomolecules requires a clear understanding of biosynthesis and degradation pathways. This view applies to most metabolites as well as other molecule types such as glycans whose repertoire is still poorly characterized. Lectins are proteins that recognize specifically and interact noncovalently with glycans. This particular class of proteins is considered as playing a major role in biology. Glycan-binding is based on multivalence, which gives lectins a unique capacity to interact with surface glycans and significantly contribute to cell-cell recognition and interactions. Lectins have been studied for many years using multiple technologies and part of the resulting information is available online in databases. Unfortunately, the connectivity of these databases with the most popular omics databases (genomics, proteomics, and glycomics) remains limited. Moreover, lectin diversity is extended and requires setting out a flexible classification that remains compatible with new sequences and 3D structures that are continuously released. We have designed UniLectin as a new insight into the knowledge of lectins, their classification, and their biological role. This platform encompasses UniLectin3D, a curated database of lectin 3D structures that follows a periodically updated classification, a set of comparative and visualizing tools and gradually released modules dedicated to specific lectins predicted in sequence databases. The second module is PropLec, focused on β-propeller lectin prediction in all species based on five distinct family profiles. This chapter describes how UniLectin can be used to explore the diversity of lectins, their 3D structures, and associated functional information as well as to perform reliable predictions of β-propeller lectins.

Unraveling the complex enzymatic machinery making a key galactolipid in chloroplast membrane: a multiscale computer simulation

Abstract: Chloroplast membranes have a high content of the uncharged galactolipids monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG). These galactolipids are essential for the biogenesis of plastids and functioning of the photosynthetic machinery. A monotopic glycosyltransferase, monogalactosyldiacylglycerol synthase synthesizes the bulk of MGDG. It is embedded in the outer leaflet of the inner envelope membrane of chloroplasts. The protein transfers a galactose residue from UDP-galactose to diacylglycerol (DAG); it needs anionic lipids such as phosphatidylglycerol (PG) to be active. The intricacy of the organization and the process of active complex assembly and synthesis have been investigated at the Coarse-Grained and All-Atom of computer simulation levels to cover large spatial and temporal scales. The following self-assembly process and catalytic events can be drawn; (1) in the membrane, in the absence of protein, there is a spontaneous formation of PG clusters to which DAG molecules associate, (2) a reorganization of the clusters occurs in the vicinity of the protein once inserted in the membrane, (3) an accompanying motion of the catalytic domain of the protein brings DAG in the proper position for the formation of the active complex MGD1/UDP-Gal/DAG/PG for which an atomistic model of interaction is proposed.

Computational tools for drawing, building and displaying carbohydrates: a visual guide.

Abstract: Drawing and visualisation of molecular structures are some of the most common tasks carried out in structural glycobiology, typically using various software. In this perspective article, we outline developments in the computational tools for the sketching, visualisation and modelling of glycans. The article also provides details on the standard representation of glycans, and glycoconjugates, which helps the communication of structure details within the scientific community. We highlight the comparative analysis of the available tools which could help researchers to perform various tasks related to structure representation and model building of glycans. These tools can be useful for glycobiologists or any researcher looking for a ready to use, simple program for the sketching or building of glycans.

Mechanism of activation of plant monogalactosyldiacylglycerol synthase 1 (MGD1) by phosphatidylglycerol.

Abstract: Mono- and digalactosyldiacylglycerol are essential galactolipids for the biogenesis of plastids and functioning of the photosynthetic machinery. In Arabidopsis, the first step of galactolipid synthesis is catalyzed by monogalactosyldiacylglycerol synthase 1 (MGD1), a monotopic protein located in the inner envelope membrane of chloroplasts, which transfers a galactose residue from UDP-galactose to diacylglycerol (DAG). MGD1 needs anionic lipids such as phosphatidylglycerol (PG) to be active, but the mechanism by which PG activates MGD1 is still unknown. Recent studies shed light on the catalytic mechanism of MGD1 and on the possible PG binding site. Particularly, Pro189 was identified as a potential residue implicated in PG binding and His155 as the putative catalytic residue. In the present study, using a multifaceted approach (Langmuir membrane models, atomic force microscopy, molecular dynamics; MD), we investigated the membrane binding properties of native MGD1 and mutants (P189A and H115A). We demonstrated that both residues are involved in PG binding, thus suggesting the existence of a PG-His catalytic dyad that should facilitate deprotonation of the nucleophile hydroxyl group of DAG acceptor. Interestingly, MD simulations showed that MGD1 induces a reorganization of lipids by attracting DAG molecules to create an optimal platform for binding.

Innovation potentials triggered by glycoscience research

Abstract: Glycoscience is an interdisciplinary field, which leads to different industrial applications derived from physicochemical and/or biological properties of carbohydrates. This study aims to evaluate how glycoscience may act as a driving force to make research innovative and sustainable in industrial and/or commercial areas. To this end, we rationalized the two main properties of carbohydrate molecules into three main value chains. The regional biomass (sugar, starch, wood) value-chain exploits the physicochemical properties of carbohydrates; the glycomics explores the biological functions of carbohydrates and the non-regional biomass (microbial, pectin, chitin) value-chain exploits the two properties. Each value-chain harbors one or more niches prone to or at an emerging stage of development, and all these niches share a techno-scientific push approach aimed at developing high value-added products with new functionalities, new bioactive glycans, and new enabling technologies that will lead to new applications and possible novel therapies and diagnostics tools.

Computational tools for drawing, building and displaying carbohydrates: a visual guide

Abstract: Drawing and visualisation of molecular structures are some of the most common tasks carried out in structural glycobiology, typically using various software. In this perspective article, we outline developments in the computational tools for the sketching, visualisation and modelling of glycans. The article also provides details on the standard representation of glycans, and glycoconjugates, which helps the communication of structure details within the scientific community. We highlight the comparative analysis of the available tools which could help researchers to perform various tasks related to structure representation and model building of glycans. These tools can be useful for glycobiologists or any researcher looking for a ready to use, simple program for the sketching or building of glycans.