1. The structure of Trametes versicolor glutathione transferase Omega 3S bound to its conjugation product glutathionyl-phenethylthiocarbamate reveals plasticity of its active site
- Author
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Thomas Perrot, Mélanie Morel-Rouhier, Mathieu Schwartz, Claude Didierjean, Eric Gelhaye, Frédérique Favier, Guillermo Mulliert, Cristallographie, Résonance Magnétique et Modélisations (CRM2), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Interactions Arbres-Microorganismes (IAM), Université de Lorraine (UL)-Institut National de la Recherche Agronomique (INRA), Region Grand Est CPER 2014-2020, University of Lorraine, Centre National de la Recherche Scientifique (CNRS), French National Research Agency (ANR) ANR-11-LAS-0002-01, Universite de Lorraine, PEPS-Mirabelle 2016, Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)
- Subjects
Models, Molecular ,Conformational change ,Phenethyl isothiocyanate ,Stereochemistry ,liaison hydrophobe ,[SDV]Life Sciences [q-bio] ,Context (language use) ,champignon lignivore ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,trametes versicolor ,Isothiocyanates ,glutathione transferase ,Transferase ,Binding site ,glutathion ,Molecular Biology ,polyphenols ,030304 developmental biology ,X-ray crystallography ,Trametes ,0303 health sciences ,Binding Sites ,Molecular Structure ,biology ,wood destroying fungi ,030302 biochemistry & molecular biology ,Active site ,Glutathione ,chemistry ,Isothiocyanate ,Biocatalysis ,biology.protein ,Protein Structure Reports ,isothiocyanate - Abstract
Trametes versicolor glutathione transferase Omega 3S (TvGSTO3S) catalyzes the conjugation of isothiocyanates (ITC) with glutathione (GSH).Previously, this isoform was investigated in depth both biochemically and structurally. Structural analysis of complexes revealed the presence of a GSH binding site (G site) and a deep hydrophobic binding site (H site) able to bind plant polyphenols. In the present study, crystals of apo TvGSTO3S were soaked with glutathionyl-phenethylthiocarbamate, the product of the reaction between GSH and phenethyl isothiocyanate (PEITC).On the basis of this crystal structure, we show that the phenethyl moiety binds in a new site at loop beta(2)-alpha(2) while the glutathionyl part exhibits a particular conformation that occupies both the G site and the entrance to the H site. This binding mode is allowed by a conformational change of the loop beta(2)-alpha(2) at the enzyme active site. It forms a hydrophobic slit that stabilizes the phenethyl group at a distinct site from the previously described H site.Structural comparison of TvGSTO3S with drosophila DmGSTD2 suggests that this flexible loop could be the region that binds PEITC for both isoforms. These structural features are discussed in a catalytic context.
- Published
- 2019
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