9BXH

OvsM from Marinimicrobium koreense, a SAM-dependent N-methyltransferase involved in ovoselenol biosynthesis

Summary for 9BXH

• Entry DOI: 10.2210/pdb9bxh/pdb
• Descriptor: 5-selenohistidine N-methyltransferase OvsM, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: ovoselenol, 5-selenohistidine, s-adenosyl-l-methionine, n-methyltransferase, transferase
• Biological source: Marinimicrobium koreense
• Total number of polymer chains: 1
• Total formula weight: 30184.03

Authors

Ireland, K.A.,Davis, K.M. (deposition date: 2024-05-22, release date: 2025-01-08, Last modification date: 2025-03-19)

Primary citation

Ireland, K.A.,Kayrouz, C.M.,Abbott, M.L.,Seyedsayamdost, M.R.,Davis, K.M.
Structural and functional analysis of SAM-dependent N-methyltransferases involved in ovoselenol and ovothiol biosynthesis.
Structure, 33:528-538.e5, 2025

PubMed Abstract: Thio/selenoimidazole Nπ-methyltransferases are an emerging family of enzymes catalyzing the final step in the production of the S/Se-containing histidine-derived antioxidants ovothiol and ovoselenol. These enzymes, prevalent in prokaryotes, show minimal sequence similarity to other methyltransferases, and the structural determinants of their reactivities remain poorly understood. Herein, we report ligand-bound crystal structures of OvsM from the ovoselenol pathway as well as a member of a previously unknown clade of standalone ovothiol-biosynthetic Nπ-methyltransferases, which we have designated OvoM. Unlike previously reported ovothiol methyltransferases, which are fused as a C-terminal domain to the sulfoxide synthase OvoA, OvoMs function independently. Comparative structural analyses reveal conserved, ligand-induced conformational changes, suggesting similar behavior in dual-domain OvoA enzymes. Mutagenesis supports a model where OvoA domain rearrangement facilitates substrate recognition via a critical Tyr residue in the domain linker. Biochemical studies identify an essential active-site Asp, likely serving as a catalytic base in the S2-like nucleophilic substitution reaction.

PubMed: 39862859
DOI: 10.1016/j.str.2024.12.020

Experimental method

X-RAY DIFFRACTION (1.48 Å)