In:
Angewandte Chemie, Wiley, Vol. 134, No. 1 ( 2022-01-03)
Abstract:
Prenyl pyrophosphate methyltransferases enhance the structural diversity of terpenoids. However, the molecular basis of their catalytic mechanisms is poorly understood. In this study, using multiple strategies, we characterized a geranyl pyrophosphate (GPP) C6‐methyltransferase, BezA. Biochemical analysis revealed that BezA requires Mg 2+ and solely methylates GPP. The crystal structures of BezA and its complex with S ‐adenosyl homocysteine were solved at 2.10 and 2.56 Å, respectively. Further analyses using site‐directed mutagenesis, molecular docking, molecular dynamics simulations, and quantum mechanics/molecular mechanics calculations revealed the molecular basis of the methylation reaction. Importantly, the function of E170 as a catalytic base to complete the methylation reaction was established. We also succeeded in switching the substrate specificity by introducing a W210A substitution, resulting in an unprecedented farnesyl pyrophosphate C6‐methyltransferase.
Type of Medium:
Online Resource
ISSN:
0044-8249
,
1521-3757
DOI:
10.1002/ange.202111217
Language:
English
Publisher:
Wiley
Publication Date:
2022
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505868-5
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506609-8
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514305-6
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505872-7
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1479266-7
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505867-3
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506259-7
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