Structure of Two N-Methyltransferases from the Caffeine Biosynthetic Pathway

Caffeine (1,3,7-trimethylxanthine) is a secondary metabolite produced by certain plant species and an important component of coffee (Coffea arabica and Coffea canephora) and tea (Camellia sinensis). Here we describe the structures of two S-adenosyl-L-methionine-dependent N-methyltransferases that me...

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Bibliographic Details
Published in:Plant physiology (Bethesda) 2007-06, Vol.144 (2), p.879-889
Main Authors: McCarthy, Andrew A, McCarthy, James G
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Atoms
Binding Sites
Biochemical Processes and Macromolecular Structures
Biochemistry
Biological and medical sciences
Biosynthesis
Biosynthetic Pathways - physiology
Caffeine - biosynthesis
Carboxylates
Coffea - enzymology
Enzymes
Fundamental and applied biological sciences. Psychology
Hydrogen bonds
Hydroxyls
Metabolism
Methyltransferases - chemistry
Methyltransferases - metabolism
Molecular Sequence Data
Molecules
Plant physiology and development
Protein Conformation
Proteins
Purines
Ribonucleosides - metabolism
Substrate Specificity
Theobromine - metabolism
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Summary:Caffeine (1,3,7-trimethylxanthine) is a secondary metabolite produced by certain plant species and an important component of coffee (Coffea arabica and Coffea canephora) and tea (Camellia sinensis). Here we describe the structures of two S-adenosyl-L-methionine-dependent N-methyltransferases that mediate caffeine biosynthesis in C. canephora 'robusta', xanthosine (XR) methyltransferase (XMT), and 1,7-dimethylxanthine methyltransferase (DXMT). Both were cocrystallized with the demethylated cofactor, S-adenosyl-L-cysteine, and substrate, either xanthosine or theobromine. Our structures reveal several elements that appear critical for substrate selectivity. Serine-316 in XMT appears central to the recognition of XR. Likewise, a change from glutamine-161 in XMT to histidine-160 in DXMT is likely to have catalytic consequences. A phenylalanine-266 to isoleucine-266 change in DXMT is also likely to be crucial for the discrimination between mono and dimethyl transferases in coffee. These key residues are probably functionally important and will guide future studies with implications for the biosynthesis of caffeine and its derivatives in plants.
ISSN:0032-0889
1532-2548
1532-2548
DOI:10.1104/pp.106.094854