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Caractérisation enzymatique et structurale d'une nouvelle famille d'aldéhyde déshydrogénase impliquée dans la dégradation de composés aromatiques toxiques

Abstract : Two phylogenetically and structurally unrelated families of NAD(P)-dependent aldehyde dehydrogenases (ALDH) catalyze the oxidation of aldehydes into activated or non-activated acids. These enzymes are known to be involved in many biological functions such as cellular differentiation, central metabolism, or detoxification pathways.The crystal structure of the bifunctional enzyme, 4-hydroxy-2-ketovalerate aldolase (DmpG)/acetaldehyde dehydrogenase (DpmF) from Pseudomonas sp. CF600, leads to the identification of a new ALDH family. The DmpF subunit exhibits a non-phosphorylating CoA-dependent aldehyde dehydrogenase activity while its structure belongs to the phosphorylating ALDH superfamily. The kinetics of the MhpEF orthologs from Escherichia coli and Thermomonospora curvata show that the kinetic parameters of MhpF do not depend of its oligomeric state, which is unique for an ALDH. In addition, the crystal structures of the enzyme with NAD+ or CoA, as well as the solution structure of the apoenzyme using SAXS, reveal the dynamics of the overall Rossmann fold between apo or cofactors-bound conformers, which is necessary to carry on the catalytic cycle. Finally, the catalytic mechanism and the structure of the thioacylenzyme intermediates indicate that MhpF is a hybrid between both ALDH families characterized to date
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  • HAL Id : tel-01749651, version 1

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Baptiste Fischer. Caractérisation enzymatique et structurale d'une nouvelle famille d'aldéhyde déshydrogénase impliquée dans la dégradation de composés aromatiques toxiques. Médecine humaine et pathologie. Université de Lorraine, 2012. Français. ⟨NNT : 2012LORR0306⟩. ⟨tel-01749651⟩

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