9M2M

the crystal structure of okaE

9M2M の概要

• エントリーDOI: 10.2210/pdb9m2m/pdb
• 分子名称: Iron/alpha-ketoglutarate-dependent dioxygenase okaE, COBALT (II) ION (3 entities in total)
• 機能のキーワード: akg-dependent mononuclear nonheme iron enzymes, multiple functions, oxidoreductase
• 由来する生物種: Penicillium simplicissimum
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 134088.14

構造登録者

Liu, T.H.,Yan, W.P.,Wang, X.Y. (登録日: 2025-02-27, 公開日: 2026-03-04, 最終更新日: 2026-04-08)

主引用文献

Wang, X.,Yu, J.,Liu, T.,Zhang, X.,Ju, M.,Xie, Z.,Naowarojna, N.,Ping, L.,Dong, Y.,Gong, B.,Xie, Y.,Nie, Y.,Hsiang, T.,Wu, R.,Zhang, L.,Liu, P.,Zhu, G.,Yan, W.,Liu, X.
Structural and mechanistic insights into azetidine-associated alpha KG-NHFe enzyme OkaE with multifunctional catalysis.
Nat Commun, 17:-, 2026

PubMed Abstract: α-Ketoglutarate-dependent mononuclear non-haem iron (αKG-NHFe) enzymes are catalytically versatile, yet OkaE is unique for synthesizing azetidine rings via C-C bond formation. Here, we report the unexpected multifunctionality of OkaE, which catalyzes sequential oxidations. Isotopic labelling studies demonstrate that a second O₂ molecule participates in sequential epoxidation and ring cleavage, incorporating two oxygen atoms within a single catalytic cycle to form the previously unknown structure, neuokaramine IV. Crystal structures of the OkaE•Co•αKG•okaramine A complex unveil a unique methionine-π interaction network that facilitates substrate binding. Mutational and crystallographic analyses suggest this network fine-tunes substrate orientation relative to the metallo-centre, activating distinct reaction pathways at the 3a-OH or C8a positions. QM/MM simulations indicate that dynamic rotation of the Fe=O species initiates the cycle, enabling reaction bifurcation. This study elucidates the structural and mechanistic basis of OkaE's reactivity, highlighting its potential as a programmable biocatalyst for natural product diversification.

PubMed: 41702921
DOI: 10.1038/s41467-026-69519-5

実験手法

X-RAY DIFFRACTION (2.2 Å)