7ETL

The crystal structure of FtmOx1-Y68F

Summary for 7ETL

• Entry DOI: 10.2210/pdb7etl/pdb
• Descriptor: Verruculogen synthase, COBALT (II) ION, SULFATE ION, ... (8 entities in total)
• Functional Keywords: non-heme iron enzyme, endoperoxide, mutant, oxidoreductase
• Biological source: Aspergillus fumigatus
• Total number of polymer chains: 2
• Total formula weight: 70837.56

Authors

Zhou, J.H.,Wu, L. (deposition date: 2021-05-13, release date: 2021-12-01, Last modification date: 2023-11-29)

Primary citation

Wu, L.,Wang, Z.,Cen, Y.,Wang, B.,Zhou, J.
Structural Insight into the Catalytic Mechanism of the Endoperoxide Synthase FtmOx1.
Angew.Chem.Int.Ed.Engl., 61:e202112063-e202112063, 2022

PubMed Abstract: The 2-oxoglutarate (2OG)-dependent non-heme enzyme FtmOx1 catalyzes the endoperoxide biosynthesis of verruculogen. Although several mechanistic studies have been carried out, the catalytic mechanism of FtmOx1 is not well determined owing to the lack of a reliable complex structure of FtmOx1 with fumitremorgin B. Herein we provide the X-ray crystal structure of the ternary complex FtmOx1⋅2OG⋅fumitremorgin B at a resolution of 1.22 Å. Our structures show that the binding of fumitremorgin B induces significant compression of the active pocket and that Y68 is in close proximity to C26 of the substrate. Further MD simulation and QM/MM calculations support a CarC-like mechanism, in which Y68 acts as the H atom donor for quenching the C26-centered substrate radical. Our results are consistent with all available experimental data and highlight the importance of accurate complex structures in the mechanistic study of enzymatic catalysis.

PubMed: 34796596
DOI: 10.1002/anie.202112063

Experimental method

X-RAY DIFFRACTION (1.99212801333 Å)