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Diversité structurale des Glutathion Transférases fongiques des classes Oméga et Xi et identification de leurs ligands par des approches cristallographiques

Abstract : The ubiquitous biochemical process that enables each organism to cope with xenobiotics from its environment and thus ensures its survival is called detoxification. Glutathione transferases (GSTs) form a large family of enzymes divided into several classes. These enzymes participate in the detoxification phase II by conjugating the tripeptide glutathione to the molecule to be eliminated. Moreover, some GSTs are involved in non-catalytic processes such as sequestration or transport of molecules from one cellular compartment to another. Studies dedicated to the catalytic activity of GSTs have been ongoing for decades, yet precise identification of molecules targeted by GSTs remains challenging. In wood-decaying organisms, some of the GST classes have expanded with an increase of the number of isoforms encoded at the genomic level. This redundancy would reflect the diversity of the small molecules released upon wood enzymatic degradation. Through this thesis work, biochemical and structural approaches were used in order to characterize eleven GST isoforms from the saprotrophic fungus Trametes versicolor. In addition, the use of libraries of molecules helped in identifying polyphenols as a family of ligands that bind these GSTs. The molecular interaction modes were described precisely based on the resolution of numerous crystal structures. The identification of a flavonoid from an extract of the wild-cherry tree (Prunus avium) on which T. versicolor grows, was enabled by using an affinity crystallography approach. These data suggest that fungal GSTs could interact with plant polyphenols released during wood degradation
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Mathieu Schwartz. Diversité structurale des Glutathion Transférases fongiques des classes Oméga et Xi et identification de leurs ligands par des approches cristallographiques. Cristallographie. Université de Lorraine, 2018. Français. ⟨NNT : 2018LORR0124⟩. ⟨tel-01894523⟩

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