7FBO

geranyl pyrophosphate C6-methyltransferase BezA binding with S-adenosylhomocysteine

7FBO の概要

• エントリーDOI: 10.2210/pdb7fbo/pdb
• 関連するPDBエントリー: 7FBH
• 分子名称: BezA, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• 機能のキーワード: methyltransferase geranyl pyrophosphate s-adenosylhomocysteine, transferase
• 由来する生物種: Streptomyces sp. RI-18-2
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 102685.18

構造登録者

Tsutsumi, H.,Moriwaki, Y.,Terada, T.,Shimizu, K.,Katsuyama, Y.,Ohnishi, Y. (登録日: 2021-07-12, 公開日: 2021-12-01, 最終更新日: 2023-11-29)

主引用文献

Tsutsumi, H.,Moriwaki, Y.,Terada, T.,Shimizu, K.,Shin-Ya, K.,Katsuyama, Y.,Ohnishi, Y.
Structural and Molecular Basis of the Catalytic Mechanism of Geranyl Pyrophosphate C6-Methyltransferase: Creation of an Unprecedented Farnesyl Pyrophosphate C6-Methyltransferase.
Angew.Chem.Int.Ed.Engl., 61:e202111217-e202111217, 2022

PubMed 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 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.

PubMed: 34626048
DOI: 10.1002/anie.202111217

実験手法

X-RAY DIFFRACTION (2.56 Å)