8YSB

Crystal structure of DynA1, a putative monoxygenase from Mivromonospora chersina.

8YSB の概要

• エントリーDOI: 10.2210/pdb8ysb/pdb
• 分子名称: Predicted ester cyclase (1 entity in total)
• 機能のキーワード: anthraquinone-fused enediyne, two-enzyme system, anthraquinone formation, oxidoreductase, isomerase
• 由来する生物種: Micromonospora chersina
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15708.98

構造登録者

Yan, X.F.,Huang, H.W.,Gao, Y.G.,Liang, Z.X. (登録日: 2024-03-22, 公開日: 2024-09-04, 最終更新日: 2024-09-11)

主引用文献

Ma, G.L.,Liu, W.Q.,Huang, H.,Yan, X.F.,Shen, W.,Visitsatthawong, S.,Prakinee, K.,Tran, H.,Fan, X.,Gao, Y.G.,Chaiyen, P.,Li, J.,Liang, Z.X.
An Enzymatic Oxidation Cascade Converts delta-Thiolactone Anthracene to Anthraquinone in the Biosynthesis of Anthraquinone-Fused Enediynes.
Jacs Au, 4:2925-2935, 2024

PubMed Abstract: Anthraquinone-fused enediynes are anticancer natural products featuring a DNA-intercalating anthraquinone moiety. Despite recent insights into anthraquinone-fused enediyne (AQE) biosynthesis, the enzymatic steps involved in anthraquinone biogenesis remain to be elucidated. Through a combination of and studies, we demonstrated that a two-enzyme system, composed of a flavin adenine dinucleotide (FAD)-dependent monooxygenase (DynE13) and a cofactor-free enzyme (DynA1), catalyzes the final steps of anthraquinone formation by converting δ-thiolactone anthracene to hydroxyanthraquinone. We showed that the three oxygen atoms in the hydroxyanthraquinone originate from molecular oxygen (O), with the sulfur atom eliminated as HS. We further identified the key catalytic residues of DynE13 and A1 by structural and site-directed mutagenesis studies. Our data support a catalytic mechanism wherein DynE13 installs two oxygen atoms with concurrent desulfurization and decarboxylation, whereas DynA1 acts as a cofactor-free monooxygenase, installing the final oxygen atom in the hydroxyanthraquinone. These findings establish the indispensable roles of DynE13 and DynA1 in AQE biosynthesis and unveil novel enzymatic strategies for anthraquinone formation.

PubMed: 39211597
DOI: 10.1021/jacsau.4c00279

実験手法

X-RAY DIFFRACTION (2.3 Å)