Structures of two natural product methyltransferases reveal the basis for substrate specificity in plant O-methyltransferases.
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 A 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 A. 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.
Structural Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
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D000595:Amino Acid Sequence; D001665:Binding Sites; D002394:Catechol O-Methyltransferase / Q000737:chemistry; D002599:Chalcone / Q000031:analogs & derivatives* / Q000378:metabolism; D047188:Chalcones; D002855:Chromatography, Thin Layer; D018360:Crystallography, X-Ray; D015257:DNA-Cytosine Methylases / Q000737:chemistry; D019281:Dimerization; D006639:Histidine / Q000235:genetics / Q000378:metabolism; D006900:Hydroxylation; D007529:Isoflavones / Q000378:metabolism; D000455:Medicago sativa / Q000201:enzymology*; D008780:Methyltransferases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D016415:Sequence Alignment; D013379:Substrate Specificity
D047188:Chalcones; D007529:Isoflavones; D006639:Histidine; D002599:Chalcone; D012435:S-Adenosylhomocysteine; C040920:isoliquiritigenin; C037664:DNA modification methylase HhaI; D015257:DNA-Cytosine Methylases; D008780:Methyltransferases; C021452:isoflavone O4'-methyltransferase; D002394:Catechol O-Methyltransferase