8G5T

Crystal structure of apo TnmK2

8G5T の概要

• エントリーDOI: 10.2210/pdb8g5t/pdb
• 分子名称: TnmK2 (2 entities in total)
• 機能のキーワード: biosynthesis, natural product, tiancimycin, enediyne, biosynthetic protein
• 由来する生物種: Streptomyces sp. CB03234
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 214313.44

構造登録者

Liu, Y.-C.,Gui, C.,Shen, B. (登録日: 2023-02-14, 公開日: 2023-10-18, 最終更新日: 2024-02-14)

主引用文献

Gui, C.,Kalkreuter, E.,Liu, Y.C.,Li, G.,Steele, A.D.,Yang, D.,Chang, C.,Shen, B.
Cofactorless oxygenases guide anthraquinone-fused enediyne biosynthesis.
Nat.Chem.Biol., 20:243-250, 2024

PubMed Abstract: The anthraquinone-fused enediynes (AFEs) combine an anthraquinone moiety and a ten-membered enediyne core capable of generating a cytotoxic diradical species. AFE cyclization is triggered by opening the F-ring epoxide, which is also the site of the most structural diversity. Previous studies of tiancimycin A, a heavily modified AFE, have revealed a cryptic aldehyde blocking installation of the epoxide, and no unassigned oxidases could be predicted within the tnm biosynthetic gene cluster. Here we identify two consecutively acting cofactorless oxygenases derived from methyltransferase and α/β-hydrolase protein folds, TnmJ and TnmK2, respectively, that are responsible for F-ring tailoring in tiancimycin biosynthesis by comparative genomics. Further biochemical and structural characterizations reveal that the electron-rich AFE anthraquinone moiety assists in catalyzing deformylation, epoxidation and oxidative ring cleavage without exogenous cofactors. These enzymes therefore fill important knowledge gaps for the biosynthesis of this class of molecules and the underappreciated family of cofactorless oxygenases.

PubMed: 37945897
DOI: 10.1038/s41589-023-01476-2

実験手法

X-RAY DIFFRACTION (1.846 Å)