7OLT
Dioxygenase AsqJ in complex with 2 and Tris
Summary for 7OLT
| Entry DOI | 10.2210/pdb7olt/pdb |
| Related | 5DAP |
| Descriptor | Iron/alpha-ketoglutarate-dependent dioxygenase asqJ, NICKEL (II) ION, 4-Methoxydehydrocyclopeptin, ... (8 entities in total) |
| Functional Keywords | quinolone biosynthesis, molecular engineering, epoxidation, catalytic mechanism, oxidoreductase |
| Biological source | Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans) |
| Total number of polymer chains | 1 |
| Total formula weight | 34702.38 |
| Authors | Auman, D.,Mader, S.L.,Ecker, F.,Dorst, K.,Braeuer, A.,Widmalm, G.,Groll, M.,Kaila, V.R.I. (deposition date: 2021-05-20, release date: 2022-06-01, Last modification date: 2024-01-31) |
| Primary citation | Auman, D.,Ecker, F.,Mader, S.L.,Dorst, K.M.,Brauer, A.,Widmalm, G.,Groll, M.,Kaila, V.R.I. Peroxy Intermediate Drives Carbon Bond Activation in the Dioxygenase AsqJ. J.Am.Chem.Soc., 144:15622-15632, 2022 Cited by PubMed Abstract: Dioxygenases catalyze stereoselective oxygen atom transfer in metabolic pathways of biological, industrial, and pharmaceutical importance, but their precise chemical principles remain controversial. The α-ketoglutarate (αKG)-dependent dioxygenase AsqJ synthesizes biomedically active quinolone alkaloids via desaturation and subsequent epoxidation of a carbon-carbon bond in the cyclopeptin substrate. Here, we combine high-resolution X-ray crystallography with enzyme engineering, quantum-classical (QM/MM) simulations, and biochemical assays to describe a peroxidic intermediate that bridges the substrate and active site metal ion in AsqJ. Homolytic cleavage of this moiety during substrate epoxidation generates an activated high-valent ferryl (Fe = O) species that mediates the next catalytic cycle, possibly without the consumption of the metabolically valuable αKG cosubstrate. Our combined findings provide an important understanding of chemical bond activation principles in complex enzymatic reaction networks and molecular mechanisms of dioxygenases. PubMed: 35980821DOI: 10.1021/jacs.2c05650 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
Download full validation report
