8PNU

Cryo-EM structure of styrene oxide isomerase bound to benzylamine inhibitor

8PNU の概要

• エントリーDOI: 10.2210/pdb8pnu/pdb
• EMDBエントリー: 17785
• 分子名称: Styrene oxide isomerase, Nanobody, BENZYLAMINE, ... (5 entities in total)
• 機能のキーワード: heme binding protein, enzyme, isomerase, membrane protein
• 由来する生物種: Pseudomonas sp. VLB120; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 206759.88

構造登録者

Khanppnavar, B.,Korkhov, V.,Li, X. (登録日: 2023-07-02, 公開日: 2024-04-03, 最終更新日: 2025-07-09)

主引用文献

Khanppnavar, B.,Choo, J.P.S.,Hagedoorn, P.L.,Smolentsev, G.,Stefanic, S.,Kumaran, S.,Tischler, D.,Winkler, F.K.,Korkhov, V.M.,Li, Z.,Kammerer, R.A.,Li, X.
Structural basis of the Meinwald rearrangement catalysed by styrene oxide isomerase.
Nat.Chem., 16:1496-1504, 2024

PubMed Abstract: Membrane-bound styrene oxide isomerase (SOI) catalyses the Meinwald rearrangement-a Lewis-acid-catalysed isomerization of an epoxide to a carbonyl compound-and has been used in single and cascade reactions. However, the structural information that explains its reaction mechanism has remained elusive. Here we determine cryo-electron microscopy (cryo-EM) structures of SOI bound to a single-domain antibody with and without the competitive inhibitor benzylamine, and elucidate the catalytic mechanism using electron paramagnetic resonance spectroscopy, functional assays, biophysical methods and docking experiments. We find ferric haem b bound at the subunit interface of the trimeric enzyme through H58, where Fe(III) acts as the Lewis acid by binding to the epoxide oxygen. Y103 and N64 and a hydrophobic pocket binding the oxygen of the epoxide and the aryl group, respectively, position substrates in a manner that explains the high regio-selectivity and stereo-specificity of SOI. Our findings can support extending the range of epoxide substrates and be used to potentially repurpose SOI for the catalysis of new-to-nature Fe-based chemical reactions.

PubMed: 38744914
DOI: 10.1038/s41557-024-01523-y

実験手法

ELECTRON MICROSCOPY (2.12 Å)