Biocristallographie & Modélisation à très haute résolution

Logo BioModLe groupe BioMod rassemble un ensemble de chercheurs avec des compétences complémentaires pour étudier les relations structure-fonction des biomolécules. D’une part, les méthodes de la biologie structurales (RMN, Diffraction des rayons X, modélisation par homologie, dynamique moléculaire, …) sont utilisées pour déterminer la structure tridimensionnelle d’enzymes et analyser leurs propriétés catalytiques. D’autre part, des méthodes originales, utilisant la densité de charge multipolaire obtenue en cristallographie à résolution ultra-haute, sont développées pour déterminer de façon précise les propriétés électrostatiques des biomolécules. Dans ce cadre plusieurs programmes sont développés : MoProSuite permettant l’affinement de la densité de charge multipolaire et MoproViewer qui est outil performant pour visualiser de façon précise les interactions moléculaires. Dans un consortium de biologistes, biochimistes et chimistes, l’équipe BioMod travaille sur plusieurs familles d’enzymes et petites molécules organiques présentant des applications potentielles dans le domaine de la santé et de l’agronomie.

Structure-function relationships

Fungal glutathione transferases
Fungi have a strong effect on plant health. On one hand, symbionts (such as mycorrhizae) canbiomod_img1 amplify yield of plant feedstock, on the other hand pathogens can have dramatic negative consequences on crops. The recent release of several fungi genome sequences allows understanding of the mechanisms of their interaction with plants and identifying the enzymes involved, for example, in the wood degradation process (Eastwood et al. 2011). Our analysis is focused on glutathione transferases (GSTs) which constitute a complex and widespread superfamily classified as enzymes of secondary metabolism.

Plant Glutaredoxins
Recent studies revealed that glutaredoxins (Grxs) constitute a multi-faceted protein family, involved not only in oxidative stress response but also in other essential functions such as iron-sulphur assembly and haem biosynthesis. These discoveries also led to propose a new classification extended to six classes (Couturier et al., Cell Mol Life Sci. 2009, 66, 2539-57).

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Molecular modelling at ultra high resolution

An extensive survey of Cambridge Structural Database is carried out to study the directionality andbiomod_img6 stereochemistry of hydrogen bonds with an oxygen acceptor including carbonyl, alcohols, phenols, ethers and esters groups. The results obtained through this survey are correlated with the charge density of these different chemical groups. The electron density of these different oxygen atoms types show striking dissimilarities in the electron lone pairs configuration.

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Software MoProSuite

The refinement program MoPro (Molecular Properties) is dedicated to the charge-densitybiomod_img8 refinement at (sub)atomic resolution of structures ranging from small molecules to biological macromolecules. MoPro uses the multipolar pseudo-atom model for the electron-density refinement. Alternative methods are also proposed, such as modelling bonding and lone-pair electron density by virtual spherical atoms.

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