6GGI

Crystal structure of CotB2 in complex with 2-fluoro-3,7,18-dolabellatriene

6GGI の概要

• エントリーDOI: 10.2210/pdb6ggi/pdb
• 分子名称: Cyclooctat-9-en-7-ol synthase, MAGNESIUM ION, PYROPHOSPHATE, ... (10 entities in total)
• 機能のキーワード: terpene synthase, cyclooctatin, lyase
• 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: 75370.85

構造登録者

Driller, R.,Janke, S.,Fuchs, M.,Warner, E.,Mhashal, A.R.,Major, D.T.,Christmann, M.,Brueck, T.,Loll, B. (登録日: 2018-05-03, 公開日: 2018-10-10, 最終更新日: 2024-01-17)

主引用文献

Driller, R.,Janke, S.,Fuchs, M.,Warner, E.,Mhashal, A.R.,Major, D.T.,Christmann, M.,Bruck, T.,Loll, B.
Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis.
Nat Commun, 9:3971-3971, 2018

PubMed Abstract: Terpenes constitute the largest and structurally most diverse natural product family. Most terpenoids exhibit a stereochemically complex macrocyclic core, which is generated by C-C bond forming of aliphatic oligo-prenyl precursors. This reaction is catalysed by terpene synthases (TPSs), which are capable of chaperoning highly reactive carbocation intermediates through an enzyme-specific reaction. Due to the instability of carbocation intermediates, the proteins' structural dynamics and enzyme:substrate interactions during TPS catalysis remain elusive. Here, we present the structure of the diterpene synthase CotB2, in complex with an in crystallo cyclised abrupt reaction product and a substrate-derived diphosphate. We captured additional snapshots of the reaction to gain an overview of CotB2's catalytic mechanism. To enhance insights into catalysis, structural information is augmented with multiscale molecular dynamic simulations. Our data represent fundamental TPS structure dynamics during catalysis, which ultimately enable rational engineering towards tailored terpene macrocycles that are inaccessible by conventional chemical synthesis.

PubMed: 30266969
DOI: 10.1038/s41467-018-06325-8

実験手法

X-RAY DIFFRACTION (1.803 Å)