8KHQ

Bifunctional sulfoxide synthase OvoA_Th2 in complex with histidine and cysteine

Summary for 8KHQ

• Entry DOI: 10.2210/pdb8khq/pdb
• Descriptor: 5-histidylcysteine sulfoxide synthase/putative 4-mercaptohistidine N1-methyltranferase, COBALT (II) ION, HISTIDINE, ... (6 entities in total)
• Functional Keywords: metal ion binding, sulfatase-modifying, histidine oxygenase, methyltransferase, oxidoreductase
• Biological source: Hydrogenimonas thermophila
• Total number of polymer chains: 4
• Total formula weight: 342275.22

Authors

Wang, J.,Ye, K.,Wang, X.Y.,Yan, W.P. (deposition date: 2023-08-22, release date: 2023-12-06, Last modification date: 2023-12-20)

Primary citation

Wang, X.,Hu, S.,Wang, J.,Zhang, T.,Ye, K.,Wen, A.,Zhu, G.,Vegas, A.,Zhang, L.,Yan, W.,Liu, X.,Liu, P.
Biochemical and Structural Characterization of OvoA Th2 : A Mononuclear Nonheme Iron Enzyme from Hydrogenimonas thermophila for Ovothiol Biosynthesis.
Acs Catalysis, 13:15417-15426, 2023

PubMed Abstract: Ovothiol A and ergothioneine are thiol-histidine derivatives with sulfur substitutions at the δ-carbon or ε-carbon of the l-histidine imidazole ring, respectively. Both ovothiol A and ergothioneine have protective effects on many aging-related diseases, and the sulfur substitution plays a key role in determining their chemical and biological properties, while factors governing sulfur incorporation regioselectivities in ovothiol and ergothioneine biosynthesis in the corresponding enzymes (OvoA, Egt1, or EgtB) are not yet known. In this study, we have successfully obtained the first OvoA crystal structure, which provides critical information to explain their C-S bond formation regioselectivity. Furthermore, OvoA exhibits several additional activities: (1) ergothioneine sulfoxide synthase activity akin to Egt1 in ergothioneine biosynthesis; (2) cysteine dioxygenase activity using l-cysteine and l-histidine analogues as substrates; (3) cysteine dioxygenase activity upon mutation of an active site tyrosine residue (Y406). The structural insights and diverse chemistries demonstrated by OvoA pave the way for future comprehensive structure-function correlation studies.

PubMed: 38058600
DOI: 10.1021/acscatal.3c04026

Experimental method

X-RAY DIFFRACTION (2.69 Å)