7FBH

geranyl pyrophosphate C6-methyltransferase BezA

Summary for 7FBH

• Entry DOI: 10.2210/pdb7fbh/pdb
• Descriptor: BezA, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, GLYCEROL, ... (6 entities in total)
• Functional Keywords: methyltransferase geranyl pyrophosphate s-adenosylmethionine, transferase
• Biological source: Streptomyces sp. RI18
• Total number of polymer chains: 3
• Total formula weight: 102473.01

Authors

Tsutsumi, H.,Moriwaki, Y.,Terada, T.,Shimizu, K.,Katsuyama, Y.,Ohnishi, Y. (deposition date: 2021-07-10, release date: 2021-12-01, Last modification date: 2024-05-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.1 Å)