7FBO
geranyl pyrophosphate C6-methyltransferase BezA binding with S-adenosylhomocysteine
Summary for 7FBO
| Entry DOI | 10.2210/pdb7fbo/pdb |
| Related | 7FBH |
| Descriptor | BezA, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total) |
| Functional Keywords | methyltransferase geranyl pyrophosphate s-adenosylhomocysteine, transferase |
| Biological source | Streptomyces sp. RI-18-2 |
| Total number of polymer chains | 3 |
| Total formula weight | 102685.18 |
| Authors | Tsutsumi, H.,Moriwaki, Y.,Terada, T.,Shimizu, K.,Katsuyama, Y.,Ohnishi, Y. (deposition date: 2021-07-12, release date: 2021-12-01, Last modification date: 2023-11-29) |
| 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 Cited by 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: 34626048DOI: 10.1002/anie.202111217 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.56 Å) |
Structure validation
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