9JT3

Crystal structure of AbxF

Summary for 9JT3

• Entry DOI: 10.2210/pdb9jt3/pdb
• Descriptor: Glyoxalase, GLYCEROL (3 entities in total)
• Functional Keywords: diels alder reaction, lyase
• Biological source: Streptomyces sp.
• Total number of polymer chains: 2
• Total formula weight: 54254.22

Authors

Zhang, M.J.,Kong, X.D. (deposition date: 2024-10-01, release date: 2025-03-26, Last modification date: 2025-10-08)

Primary citation

Yan, X.,Jia, X.,Luo, Z.,Ji, S.,Zhang, M.J.,Zhang, H.,Yu, M.,Orts, J.,Jiang, K.,Lin, Z.,Deng, Z.,Kong, X.D.,Kobe, B.,Zhao, Y.L.,Mobli, M.,Qu, X.
An enzymatic dual-oxa Diels-Alder reaction constructs the oxygen-bridged tricyclic acetal unit of (-)-anthrabenzoxocinone.
Nat.Chem., 17:1058-1066, 2025

PubMed Abstract: The hetero-Diels-Alder (HDA) reaction is a key method for synthesizing six-membered heterocyclic rings in natural products and bioactive compounds. Despite its importance in synthetic chemistry, naturally occurring enzymatic HDA reactions are rare and limited to a single heteroatom. Here we report AbxF, a bifunctional vicinal oxygen chelate (VOC)-like protein that catalyses dehydration and dual-oxa Diels-Alder reactions to stereoselectively form the oxygen-bridged tricyclic acetal of (-)-anthrabenzoxocinone ((-)-ABX). Isotope assays and density functional theory calculations reveal a dehydration-coordinated, concerted HDA mechanism. The crystal structure of AbxF and NMR complex structures of AbxF with its substrate analogue and (-)-ABX define the reaction's structural basis. Mutational analysis identifies Asp17 as a general base that mediates dehydration, forming an o-quinone methide intermediate for stereoselective dual-oxa HDA. This work establishes the molecular and structural basis of a polyheteroatomic Diels-Alderase, paving the way for designing polyheteroatomic DA enzymatic tools.

PubMed: 40263633
DOI: 10.1038/s41557-025-01804-0

Experimental method

X-RAY DIFFRACTION (2 Å)