7DE2

iron and alpha-ketoglutarate-dependent endoperoxidase NvfI

Summary for 7DE2

• Entry DOI: 10.2210/pdb7de2/pdb
• Descriptor: NvfI, 2-OXOGLUTARIC ACID, methyl (3'~{a}~{R},4'~{S},5'~{S},5~{a}~{S},6~{S},7~{S},9~{a}~{R})-1,1,3'~{a},4',5~{a},7,7'-heptamethyl-3,6'-bis(oxidanylidene)spiro[4,5,7,8,9,9~{a}-hexahydrobenzo[c]oxepine-6,2'-4,5-dihydro-3~{H}-1-benzofuran]-5'-carboxylate, ... (5 entities in total)
• Functional Keywords: novofumigatonin, endoperoxidase, iron and alpha-ketoglutarate-dependent enzyme, oxidoreductase
• Biological source: Aspergillus novofumigatus IBT 16806
• Total number of polymer chains: 2
• Total formula weight: 68768.79

Authors

Zhai, R.,Mori, T.,Abe, I. (deposition date: 2020-11-01, release date: 2021-07-14, Last modification date: 2024-05-29)

Primary citation

Mori, T.,Zhai, R.,Ushimaru, R.,Matsuda, Y.,Abe, I.
Molecular insights into the endoperoxide formation by Fe(II)/ alpha-KG-dependent oxygenase NvfI.
Nat Commun, 12:4417-4417, 2021

PubMed Abstract: Endoperoxide-containing natural products are a group of compounds with structurally unique cyclized peroxide moieties. Although numerous endoperoxide-containing compounds have been isolated, the biosynthesis of the endoperoxides remains unclear. NvfI from Aspergillus novofumigatus IBT 16806 is an endoperoxidase that catalyzes the formation of fumigatonoid A in the biosynthesis of novofumigatonin. Here, we describe our structural and functional analyses of NvfI. The structural elucidation and mutagenesis studies indicate that NvfI does not utilize a tyrosyl radical in the reaction, in contrast to other characterized endoperoxidases. Further, the crystallographic analysis reveals significant conformational changes of two loops upon substrate binding, which suggests a dynamic movement of active site during the catalytic cycle. As a result, NvfI installs three oxygen atoms onto a substrate in a single enzyme turnover. Based on these results, we propose a mechanism for the NvfI-catalyzed, unique endoperoxide formation reaction to produce fumigatonoid A.

PubMed: 34285212
DOI: 10.1038/s41467-021-24685-6

Experimental method

X-RAY DIFFRACTION (1.9 Å)