Abstract
Chalcone O-methyltransferase (ChOMT) and isoflavone O-methyltransferase (IOMT) are S-adenosyl-l-methionine (SAM) dependent plant natural product methyltransferases involved in secondary metabolism in Medicago sativa (alfalfa). Here we report the crystal structure of ChOMT in complex with the product S-adenosyl-l-homocysteine and the substrate isoliquiritigenin (4,2′,4′-trihydroxychalcone) refined to 1.8 Å as well as the crystal structure of IOMT in complex with the products S-adenosyl-l-homocysteine and isoformononetin (4′-hydroxy-7-methoxyisoflavone) refined to 1.4 Å. These two OMTs constitute the first plant methyltransferases to be structurally characterized and reveal a novel oligomerization domain and the molecular determinants for substrate selection. As such, this work provides a structural basis for understanding the substrate specificity of the diverse family of plant OMTs and facilitates the engineering of novel activities in this extensive class of natural product biosynthetic enzymes.
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Acknowledgements
We acknowledge the assistance provided by members of the Noel group and the staff of beamlines 7-1 and 9-2 at the Stanford Synchrotron Radiation Facility. The SSRL Biotechnology Program is supported by the NIH, National Center for Research Resources, Biomedical Technology Program, and the DOE, Office of Biological and Environmental Research. This work was supported by funds from the Salk Institute and the National Science Foundation awarded to J.P.N. C.Z. was supported by funds from the NIH Molecular Biophysics Training Grant administered by the University of California, San Diego and funds from the Samuel Roberts Noble Foundation.
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Zubieta, C., He, XZ., Dixon, R. et al. Structures of two natural product methyltransferases reveal the basis for substrate specificity in plant O-methyltransferases. Nat Struct Mol Biol 8, 271–279 (2001). https://doi.org/10.1038/85029
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DOI: https://doi.org/10.1038/85029
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