8TWT

Crystal structure of nitrile synthase AetD with substrate bound and cofactor partially assembled

8TWT の概要

• エントリーDOI: 10.2210/pdb8twt/pdb
• 関連するPDBエントリー: 8TWN
• 分子名称: AetD, (2S)-2-azanyl-3-[5,7-bis(bromanyl)-1H-indol-3-yl]propanoic acid, D-MALATE, ... (7 entities in total)
• 機能のキーワード: nitrile synthase, non-heme iron enzyme, diiron enzyme, oxidoreductase
• 由来する生物種: Aetokthonos hydrillicola
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61994.85

構造登録者

Ye, N.,Drennan, C.L. (登録日: 2023-08-21, 公開日: 2024-08-28, 最終更新日: 2024-12-18)

主引用文献

Adak, S.,Ye, N.,Calderone, L.A.,Duan, M.,Lubeck, W.,Schafer, R.J.B.,Lukowski, A.L.,Houk, K.N.,Pandelia, M.E.,Drennan, C.L.,Moore, B.S.
A single diiron enzyme catalyses the oxidative rearrangement of tryptophan to indole nitrile.
Nat.Chem., 16:1989-1998, 2024

PubMed Abstract: Nitriles are uncommon in nature and are typically constructed from oximes through the oxidative decarboxylation of amino acid substrates or from the derivatization of carboxylic acids. Here we report a third nitrile biosynthesis strategy featuring the cyanobacterial nitrile synthase AetD. During the biosynthesis of the eagle-killing neurotoxin, aetokthonotoxin, AetD transforms the 2-aminopropionate portion of 5,7-dibromo-L-tryptophan to a nitrile. Employing a combination of structural, biochemical and biophysical techniques, we characterized AetD as a non-haem diiron enzyme that belongs to the emerging haem-oxygenase-like dimetal oxidase superfamily. High-resolution crystal structures of AetD together with the identification of catalytically relevant products provide mechanistic insights into how AetD affords this unique transformation, which we propose proceeds via an aziridine intermediate. Our work presents a unique template for nitrile biogenesis and portrays a substrate binding and metallocofactor assembly mechanism that may be shared among other haem-oxygenase-like dimetal oxidase enzymes.

PubMed: 39285206
DOI: 10.1038/s41557-024-01603-z

実験手法

X-RAY DIFFRACTION (2.3 Å)