9J1H

The binary complex structure of F2Y224-FtmOx1 mutant with alpha-ketoglutarate

9J1H の概要

• エントリーDOI: 10.2210/pdb9j1h/pdb
• 分子名称: Verruculogen synthase, COBALT (II) ION, 2-OXOGLUTARIC ACID, ... (6 entities in total)
• 機能のキーワード: dioxygenase, non-heme, iron dependent, oxidoreductase
• 由来する生物種: Aspergillus fumigatus Af293 (Neosartorya fumigata)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70834.23

構造登録者

Wang, X.Y.,Wang, J.,Yan, W.P. (登録日: 2024-08-05, 公開日: 2025-03-19)

主引用文献

Wang, X.,Yang, L.,Wang, S.,Wang, J.,Li, K.,Naowarojna, N.,Ju, Y.,Ye, K.,Han, Y.,Yan, W.,Liu, X.,Zhang, L.,Liu, P.
Characterizing Y224 conformational flexibility in FtmOx1-catalysis using 19 F NMR spectroscopy.
Catalysis Science And Technology, 15:386-395, 2025

PubMed Abstract: α-Ketoglutarate-dependent non-haem iron (αKG-NHFe) enzymes play a crucial role in natural product biosynthesis, and in some cases exhibiting multifunctional catalysis capability. This study focuses on αKG-NHFe enzyme FtmOx1, which catalyzes endoperoxidation, dealkylation, and alcohol oxidation reactions in verruculogen biosynthesis. We explore the hypothesis that the conformational dynamics of the active site Y224 confer the multifunctional activities of FtmOx1-catalysis. Utilizing Y224-to-3,5-difluorotyrosine-substituted FtmOx1, produced the amber codon suppression method, we conducted F NMR characterization to investigate FtmOx1's structural flexibility. Subsequent biochemical and X-ray crystallographic analyses provided insights into how specific conformations of FtmOx1-substrate complexes influence their catalytic activities. These findings underscore the utility of F NMR as a powerful tool for elucidating the complex mechanisms of multifunctional enzymes, offering potential avenues for developing biocatalytic processes to produce novel therapeutic agents harnessing their unique catalytic properties.

PubMed: 39669701
DOI: 10.1039/d4cy01077a

実験手法

X-RAY DIFFRACTION (2 Å)