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

Patricia Amara, Claire Saragaglia, Jean-Marie Mouesca, Lydie Martin and Yvain Nicolet ()
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Patricia Amara: Univ. Grenoble Alpes, CEA, CNRS, IBS, Metalloproteins Unit
Claire Saragaglia: Univ. Grenoble Alpes, CEA, CNRS, IBS, Metalloproteins Unit
Jean-Marie Mouesca: Univ. Grenoble Alpes, CEA, CNRS, IRIG-DIESE-SyMMES-CAMPE
Lydie Martin: Univ. Grenoble Alpes, CEA, CNRS, IBS, Metalloproteins Unit
Yvain Nicolet: Univ. Grenoble Alpes, CEA, CNRS, IBS, Metalloproteins Unit

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29980-4

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