9WIU

SbSOMT in apo state

Summary for 9WIU

• Entry DOI: 10.2210/pdb9wiu/pdb
• Descriptor: O-methyltransferase domain-containing protein, TETRAETHYLENE GLYCOL, DI(HYDROXYETHYL)ETHER, ... (8 entities in total)
• Functional Keywords: methyltransferase, plant o-methyltransferase, sbsomt, stilbene o-methyltransferase, transferase
• Biological source: Sorghum bicolor (sorghum)
• Total number of polymer chains: 6
• Total formula weight: 244919.25

Authors

Pow, K.C.,Hao, Q. (deposition date: 2025-08-29, release date: 2026-06-17)

Primary citation

Pow, K.C.,Zhang, N.,Yan, M.,Wang, X.,Lui, A.C.W.,Lo, C.,Hao, Q.
Structural dynamics of the pi-stacking network governing cofactor-substrate cooperativity of SbSOMT methyltransferase.
Commun Chem, 2026

PubMed Abstract: SAM-dependent methyltransferases are enzymes that catalyze the transfer of a methyl group from a cofactor to a substrate through an ordered or random sequential bi-bi mechanism. However, the structural dynamics governing binding cooperativity between the cofactor and substrate remain understudied. In this study, we demonstrate that SbSOMT, a plant O-methyltransferase, exhibits bilateral positive cooperativity between the cofactor and substrate, except the unproductive SbSOMT-SAM-pterostilbene complex. Furthermore, SbSOMT displayed substrate-binding kinetics that shift in response to the nature of bound-cofactor. Sinefungin-bound SbSOMT exhibited positive cooperativity primarily attributed to an increased substrate association rate constant (k), whereas SAH-bound SbSOMT displayed positive cooperativity driven primarily by a decreased dissociation rate constant (k). Structural analysis implies that these cooperativity switch and divergent binding kinetics stem from the interactions between the cofactor and substrate at the methyl binding site. Integrating structural insights reveals that a dynamic W279 π-stacking network governs this cooperativity. Upon binding of the first ligand, H196, W279, and H282 rearrange to form a π-stacking network, in which W279 serves as the essential central plane that also stacks with the substrate. Accordingly, W279A mutagenesis substantially impaired the substrate affinity, cooperativity and enzymatic activity.

PubMed: 42259925
DOI: 10.1038/s42004-026-02087-3

Experimental method

X-RAY DIFFRACTION (2.04 Å)