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Updated: Jun 23, 2026

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
Structural and Mechanistic Insights into the O‑Methyltransferase McbD in Marinacarboline Biosynthesis
Zhi Qiao1, Xiaona Yang1, Jiaozhuang Liu1
1School of Life Sciences, Anhui Medical University, Hefei 230032, China.
Abstract:
O-Methylation represents a prevalent tailoring modification in natural product biosynthesis, significantly altering molecular properties and bioactivity. In this study, we report the crystal structure of the O-methyltransferase (MTase) McbD in complex with S-adenosyl-l-homocysteine (SAH) at 3.0 Å resolution, complemented by a modeled binding pose for the substrate marinacarboline B (1). Through integrated site-directed mutagenesis and enzymatic assays, we identified critical residues required for catalytic activity and propose a refined mechanistic model for methyl transfer. These findings offer substantive structural and mechanistic insights into how O-MTases drive the diversification of bioactive natural products.
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