7E5V

Crystal structure of Phm7 in complex with inhibitor

7E5V の概要

• エントリーDOI: 10.2210/pdb7e5v/pdb
• 分子名称: Diels-Alderase, [(1S,2S,5R)-5-methyl-2-propan-2-yl-cyclohexyl]methanamine, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: cyclase, diels-alderase, diels alder, [4+2] cycloaddition, biosynthetic protein
• 由来する生物種: Pyrenochaetopsis sp.
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 128214.91

構造登録者

Fujiyama, K.,Kato, N.,Kinugasa, K.,Hino, T.,Takahashi, S.,Nagano, S. (登録日: 2021-02-20, 公開日: 2021-06-30, 最終更新日: 2024-04-03)

主引用文献

Fujiyama, K.,Kato, N.,Re, S.,Kinugasa, K.,Watanabe, K.,Takita, R.,Nogawa, T.,Hino, T.,Osada, H.,Sugita, Y.,Takahashi, S.,Nagano, S.
Molecular Basis for Two Stereoselective Diels-Alderases that Produce Decalin Skeletons*.
Angew.Chem.Int.Ed.Engl., 60:22401-22410, 2021

PubMed Abstract: Enzymes catalyzing [4+2] cycloaddition have attracted increasing attention because of their key roles in natural product biosynthesis. Here, we solved the X-ray crystal structures of a pair of decalin synthases, Fsa2 and Phm7, that catalyze intramolecular [4+2] cycloadditions to form enantiomeric decalin scaffolds during biosynthesis of the HIV-1 integrase inhibitor equisetin and its stereochemical opposite, phomasetin. Computational modeling, using molecular dynamics simulations as well as quantum chemical calculations, demonstrates that the reactions proceed through synergetic conformational constraints assuring transition state-like substrates folds and their stabilization by specific protein-substrate interactions. Site-directed mutagenesis experiments verified the binding models. Intriguingly, the flexibility of bound substrates is largely different in two enzymes, suggesting the distinctive mechanism of dynamics regulation behind these stereoselective reactions. The proposed reaction mechanism herein deepens the basic understanding how these enzymes work but also provides a guiding principle to create artificial enzymes.

PubMed: 34121297
DOI: 10.1002/anie.202106186

実験手法

X-RAY DIFFRACTION (1.61 Å)