L-tyrosine-bound ThiH structure reveals C–C bond break differences within radical SAM aromatic amino acid lyases - Université Grenoble Alpes Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2022

L-tyrosine-bound ThiH structure reveals C–C bond break differences within radical SAM aromatic amino acid lyases

Résumé

Abstract 2-iminoacetate synthase ThiH is a radical S -adenosyl-L-methionine (SAM) L-tyrosine lyase and catalyzes the L-tyrosine Cα–Cβ bond break to produce dehydroglycine and p -cresol while the radical SAM L-tryptophan lyase NosL cleaves the L-tryptophan Cα–C bond to produce 3-methylindole-2-carboxylic acid. It has been difficult to understand the features that condition one C–C bond break over the other one because the two enzymes display significant primary structure similarities and presumably similar substrate-binding modes. Here, we report the crystal structure of L-tyrosine bound ThiH from Thermosinus carboxydivorans revealing an unusual protonation state of L-tyrosine upon binding. Structural comparison of ThiH with NosL and computational studies of the respective reactions they catalyze show that substrate activation is eased by tunneling effect and that subtle structural changes between the two enzymes affect, in particular, the hydrogen-atom abstraction by the 5´-deoxyadenosyl radical species, driving the difference in reaction specificity.

Dates et versions

hal-03669800 , version 1 (17-05-2022)

Identifiants

Citer

Patricia Amara, Claire Saragaglia, Jean-Marie Mouesca, Lydie Martin, Yvain Nicolet. L-tyrosine-bound ThiH structure reveals C–C bond break differences within radical SAM aromatic amino acid lyases. Nature Communications, 2022, 13 (1), pp.2284. ⟨10.1038/s41467-022-29980-4⟩. ⟨hal-03669800⟩
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