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Publication Abstract from PubMed

The 2-oxoglutarate (2OG)-dependent non-heme FtmOx1 catalyzes the endoperoxide biosynthesis of verruculogen. Although several mechanistic studies have been carried out, the catalytic mechanism of FtmOx1 is not well determined due to the lack of the reliable complex structure of FtmOx1 with fumitremorgin B. Here we provided the X-ray structure of the ternary complex FtmOx1*2OG*fumitremorgin B at resolution of 1.22 A. Our structures show that the binding of fumitremorgin B has induced the significant compression of the active pocket and Y68 in close proximity to C26 of the substrate. Further MD simulation and QM/MM calculations support the CarC-like mechanism proposed by Bollinger and coworkers, in which Y68 rather than Y224 acts as the H atom donor for quenching the C26-centered substrate radical. Our work is consistent with all available experimental data and highlights the importance of the accurate complex structure in mechanistic study of enzymatic catalysis.

Structural Insight into the Catalytic Mechanism of the Endoperoxide Synthase FtmOx1.,Zhou J, Wu L, Wang Z, Cen Y, Wang B Angew Chem Int Ed Engl. 2021 Nov 18. doi: 10.1002/anie.202112063. PMID:34796596^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.