9J2P

Fe2+/pterin-dependent,BH4-L-isoleucine-SnPolE complex

9J2P の概要

• エントリーDOI: 10.2210/pdb9j2p/pdb
• 分子名称: SnPolE, FE (II) ION, ISOLEUCINE, ... (5 entities in total)
• 機能のキーワード: fe2+/pterin-dependent, oxidoreductase
• 由来する生物種: Streptomyces sp. NTH33
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 86473.37

構造登録者

Zhang, Z.Y.,Chen, W.Q.,Wang, B.J.,Qu, Y.,Gong, R.,Liu, J. (登録日: 2024-08-07, 公開日: 2025-10-08, 最終更新日: 2025-10-15)

主引用文献

Gong, R.,Qu, Y.,Liu, J.,Zhang, X.,Zhou, L.,Tian, Z.,Zeng, X.,Jin, B.,Li, Z.,Yu, L.,Chen, R.,Zhou, Y.,Liao, L.,Yang, L.,Song, X.,Cai, Y.S.,Shen, K.,Deng, Z.,Zhang, Z.,Wang, B.,Chen, W.
A two-metalloenzyme cascade constructs the azetidine-containing pharmacophore.
Nat.Chem., 2025

PubMed Abstract: Azetidine is a prominent pharmacophore present in dozens of drug-related molecules of both natural and synthetic origins. But how nature builds this moiety has long remained enigmatic. Here we address the full deciphering of a two-metalloenzyme cascade leading to polyoximic acid, an azetidine-containing moiety of the fungicide polyoxin. We demonstrate that the PolE enzyme functions as an Fe/pterin-dependent L-isoleucine desaturase. Moreover we illustrate that PolF is a new member of the emerging haem-oxygenase-like diiron oxidases, converting the desaturated L-isoleucine to polyoximic acid via an intramolecular C-N cyclization. Remarkably, we also establish that PolF exhibits dual functionality, orchestrating the sequential desaturation and cyclization with L-isoleucine as the initial substrate. Finally, our combined structural and quantum-mechanics/molecular-mechanics studies show that the PolF enzyme employs an extraordinary mechanism for the construction of the azetidine-containing moiety. These findings expand our knowledge on the catalysis of metalloenzymes and open the way for rational access of more azetidine-related molecules.

PubMed: 41028918
DOI: 10.1038/s41557-025-01949-y

実験手法

X-RAY DIFFRACTION (1.75 Å)