7VBQ

Heterodimer structure of Fe(II)/(alpha)ketoglutarate-dependent dioxygenase TlxIJ

7VBQ の概要

• エントリーDOI: 10.2210/pdb7vbq/pdb
• 分子名称: Fe(II)/(alpha)ketoglutarate-dependent dioxygenase TlxJ, Fe(II)/(alpha)ketoglutarate-dependent dioxygenase TlxI, N-OXALYLGLYCINE, ... (5 entities in total)
• 機能のキーワード: fe(ii)/(alpha)ketoglutarate-dependent dioxygenase, heterodimer, oxidoreductase
• 由来する生物種: Talaromyces purpureogenus; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 67896.89

構造登録者

Li, X.,Awakawa, T.,Mori, T.,Abe, I. (登録日: 2021-09-01, 公開日: 2022-04-20, 最終更新日: 2023-11-29)

主引用文献

Li, X.,Awakawa, T.,Mori, T.,Ling, M.,Hu, D.,Wu, B.,Abe, I.
Heterodimeric Non-heme Iron Enzymes in Fungal Meroterpenoid Biosynthesis.
J.Am.Chem.Soc., 143:21425-21432, 2021

PubMed Abstract: Talaromyolides (-) are a group of unusual 6/6/6/6/6/6 hexacyclic meroterpenoids with (3)-6-hydroxymellein and 4,5-seco-drimane substructures, isolated from the marine fungus . We have identified the biosynthetic gene cluster by heterologous expression in , enzyme assays, and CRISPR-Cas9-based gene inactivation. Remarkably, the heterodimer of non-heme iron (NHI) enzymes, TlxJ-TlxI, catalyzes three steps of oxidation including a key reaction, hydroxylation at C-5 and C-9 of , the intermediate with 3-ketohydroxydrimane scaffold, to facilitate a retro-aldol reaction, leading to the construction of the 4,5-secodrimane skeleton and characteristic ketal scaffold of -. The products of TlxJ-TlxI, and , were further hydroxylated at C-4'β by another NHI heterodimer, TlxA-TlxC, and acetylated by TlxB to yield the final products, and . The X-ray structural analysis coupled with site-directed mutagenesis provided insights into the heterodimer TlxJ-TlxI formation and its catalysis. This is the first report to show that two NHI proteins form a heterodimer for catalysis and utilizes a novel methodology to create functional oxygenase structures in secondary metabolite biosynthesis.

PubMed: 34881885
DOI: 10.1021/jacs.1c11548

実験手法

X-RAY DIFFRACTION (1.95 Å)