7PD1

Crystal structure of the L-tyrosine-bound radical SAM tyrosine lyase ThiH (2-iminoacetate synthase) from Thermosinus carboxydivorans

Summary for 7PD1

• Entry DOI: 10.2210/pdb7pd1/pdb
• Descriptor: Thiazole biosynthesis protein ThiH, IRON/SULFUR CLUSTER, 5'-DEOXYADENOSINE, ... (10 entities in total)
• Functional Keywords: radical sam enzyme 2-iminoacetate metalloprotein, lyase
• Biological source: Thermosinus carboxydivorans Nor1
• Total number of polymer chains: 2
• Total formula weight: 89427.16

Authors

Amara, P.,Saragaglia, C.,Mouesca, J.-M.,Martin, L.,Nicolet, Y. (deposition date: 2021-08-04, release date: 2022-05-11, Last modification date: 2024-01-31)

Primary citation

Amara, P.,Saragaglia, C.,Mouesca, J.M.,Martin, L.,Nicolet, Y.
L-tyrosine-bound ThiH structure reveals C-C bond break differences within radical SAM aromatic amino acid lyases.
Nat Commun, 13:2284-2284, 2022

PubMed 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.

PubMed: 35477710
DOI: 10.1038/s41467-022-29980-4

Experimental method

X-RAY DIFFRACTION (1.27 Å)