9RP1

Ensemble refined structure of CotB2 in complex with alendronate

9RP1 の概要

• エントリーDOI: 10.2210/pdb9rp1/pdb
• 分子名称: Cyclooctat-9-en-7-ol synthase, 4-AMINO-1-HYDROXYBUTANE-1,1-DIYLDIPHOSPHONATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: terpene synthase, cyclooctatin, diterpence synthase, hydrolase
• 由来する生物種: Streptomyces melanosporofaciens
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 74177.00

構造登録者

Helmer, C.P.O.,Loll, B. (登録日: 2025-06-23, 公開日: 2025-09-17, 最終更新日: 2026-02-25)

主引用文献

Gupta, P.K.,Helmer, C.P.O.,Ringel, M.,Loll, B.,Bruck, T.,Major, D.T.
The initial dynamics of product release in terpene synthases-The case of CotB2.
Protein Sci., 34:e70312-e70312, 2025

PubMed Abstract: Although the enzymatic mechanisms of terpene synthases have been extensively characterized through experimental and computational studies, the atomistic details underlying the product release process have remained elusive. In this study, we present the first atomistic simulations of the initial stages of product release in a terpene synthase, using the bacterial diterpene cyclase CotB2 as a model system. CotB2 catalyzes the complex cyclization of geranylgeranyl diphosphate (GGDP) to the tricyclic diterpene cyclooctat-9-en-7-ol in a single active site through an 11-step reaction cascade. Our MD simulations focus on three model systems representing CotB2 with bound GGDP and cyclooctat-9-en-7-ol, the latter in two states-with the diphosphate fully deprotonated (PO ) and protonated diphosphate (HPO ). Analysis of the MD trajectories clearly shows that product release is initiated by the dislocation of the diphosphate group, which in turn triggers active site opening via coordinated C-terminal motions. Notably, protonation of the diphosphate moiety appears to be the key event that weakens its interactions with the active site and enables product release. These findings provide crucial mechanistic insight into the final phase of terpene biosynthesis and open new avenues for rational enzyme engineering targeting product release.

PubMed: 40990851
DOI: 10.1002/pro.70312

実験手法

X-RAY DIFFRACTION (2.1 Å)