8Q22

Crystal structure of Vanadium-dependent haloperoxidase R425S mutant in complex with 1,3,5-trimethoxybenzene (A. marina)

8Q22 の概要

• エントリーDOI: 10.2210/pdb8q22/pdb
• 関連するPDBエントリー: 5LPC
• 分子名称: Vanadium-dependent bromoperoxidase, putative, PHOSPHATE ION, 1,3,5-trimethoxybenzene, ... (4 entities in total)
• 機能のキーワード: vanadium, enzyme catalysis, peroxidase, halogenation, mutant, ligand-complex, oxidoreductase
• 由来する生物種: Acaryochloris marina
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 73349.67

構造登録者

Zeides, P.,Bellmannn-Sickert, K.,Zhang, R.,Seel, C.J.,Most, V.,Schroeder, C.T.,Groll, M.,Gulder, T. (登録日: 2023-08-01, 公開日: 2024-08-14, 最終更新日: 2025-03-12)

主引用文献

Zeides, P.,Bellmann-Sickert, K.,Zhang, R.,Seel, C.J.,Most, V.,Schoeder, C.T.,Groll, M.,Gulder, T.
Unraveling the molecular basis of substrate specificity and halogen activation in vanadium-dependent haloperoxidases.
Nat Commun, 16:2083-2083, 2025

PubMed Abstract: Vanadium-dependent haloperoxidases (VHPOs) are biotechnologically valuable and operationally versatile biocatalysts. VHPOs share remarkable active-site structural similarities yet display variable reactivity and selectivity. The factors dictating substrate specificity and, thus, a general understanding of VHPO reaction control still need to be discovered. This work's strategic single-point mutation in the cyanobacterial bromoperoxidase AmVHPO facilitates a selectivity switch to allow aryl chlorination. This mutation induces loop formation that interacts with the neighboring protein monomer, creating a tunnel to the active sites. Structural analysis of the substrate-R425S-mutant complex reveals a substrate-binding site at the interface of two adjacent units. There, residues Glu139 and Phe401 interact with arenes, extending the substrate residence time close to the vanadate cofactor and stabilizing intermediates. Our findings validate the long-debated existence of direct substrate binding and provide a detailed VHPO mechanistic understanding. This work will pave the way for a broader application of VHPOs in diverse chemical processes.

PubMed: 40021637
DOI: 10.1038/s41467-025-57023-1

実験手法

X-RAY DIFFRACTION (3.3 Å)