9M2L

Crystal structure of okaE in complex with a-ketoglutarate and okaramine A at 2.5 angstroms resolution.

This is a non-PDB format compatible entry.

Summary for 9M2L

• Entry DOI: 10.2210/pdb9m2l/pdb
• Descriptor: Alpha-ketoglutarate-dependent dioxygenase, COBALT (II) ION, (1Z,4R,12S,14S,17Z)-12-hydroxy-19,19-dimethyl-5-(2-methylbut-3-en-2-yl)-3,5,16,21-tetrazaheptacyclo[14.13.0.03,14.04,12.06,11.020,28.022,27]nonacosa-1(29),6,8,10,17,20(28),22,24,26-nonaene-2,15-dione, ... (5 entities in total)
• Functional Keywords: akg-dependent mononuclear nonheme iron enzymes, multiple functions, okaramine indole alkaloids, oxidoreductase
• Biological source: Penicillium simplicissimum
• Total number of polymer chains: 4
• Total formula weight: 139794.16

Authors

Liu, T.H.,Yan, W.P. (deposition date: 2025-02-27, release date: 2026-03-04, Last modification date: 2026-03-11)

Primary citation

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, 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

Experimental method

X-RAY DIFFRACTION (2.55 Å)