8XU7

Crystal structure of Lsd18 in complex with a product

8XU7 の概要

• エントリーDOI: 10.2210/pdb8xu7/pdb
• 分子名称: Putative epoxidase LasC, FLAVIN-ADENINE DINUCLEOTIDE, (4R,5S)-3-((2R,3S,4S)-2-ethyl-5-((2R,3R)-2-ethyl-3-(2-((2R,3R)-2-ethyl-3-methyloxiran-2-yl)ethyl)oxiran-2-yl)-3-hydroxy-4-methylpentanoyl)-4-methyl-5-phenyloxazolidin-2-one, ... (5 entities in total)
• 機能のキーワード: flavin-dependent monooxygenase, epoxidation, flavoprotein
• 由来する生物種: Streptomyces lasalocidi
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 108440.36

構造登録者

Deng, Y.M.,Chen, X. (登録日: 2024-01-12, 公開日: 2025-01-15, 最終更新日: 2025-06-18)

主引用文献

Wang, Q.,Deng, Y.,Viera, D.,Liu, X.,Liu, N.,Hu, Y.,Hu, X.,Wei, H.,Zhou, Q.,Lan, T.,He, W.,Chen, X.,Kim, C.Y.
Structural Basis of Sequential Enantioselective Epoxidation by a Flavin-Dependent Monooxygenase in Lasalocid A Biosynthesis.
Angew.Chem.Int.Ed.Engl., 64:e202504982-e202504982, 2025

PubMed Abstract: Polyether polyketides are a structurally diverse group of natural products known for their antimicrobial and antiproliferative activities. Lasalocid A is a canonical natural polyether produced by the soil bacterium Streptomyces lasalocidi. In lasalocid A biosynthesis, a polyene polyketide intermediate is converted into a bisepoxide by the flavin-dependent monooxygenase enzyme Lsd18. Remarkably, Lsd18 acts on two distinct C═C groups in the substrate molecule, forming two (R,R) epoxides. We have determined the X-ray crystal structures of Lsd18 in the substrate-free, substrate-bound, and product-bound forms. Our work has revealed that Lsd18 has an extra-large substrate-binding pocket that allows the polyene to adopt different conformations within the enzyme pocket. This feature enables Lsd18 to epoxidate both of the C═C groups. Additionally, a subpocket located near the Lsd18 active site controls stereoselectivity by dictating which face of the C═C group is placed next to the flavin. Molecular understanding of how Lsd18 transforms a polyene into a bisepoxide during lasalocid A biosynthesis lays the foundation for the production of designer polyethers for drug development.

PubMed: 40199722
DOI: 10.1002/anie.202504982

実験手法

X-RAY DIFFRACTION (2.2 Å)