8W1X

2.35-angstrom resolution intermediate crystal structure of KatG from Mycobacterium tuberculosis with an MYW-OOH cofactor soaked with peroxide for 5 minutes

8W1X の概要

• エントリーDOI: 10.2210/pdb8w1x/pdb
• 分子名称: Catalase-peroxidase, PROTOPORPHYRIN IX CONTAINING FE, OXYGEN MOLECULE, ... (8 entities in total)
• 機能のキーワード: met-tyr-trp cofactor, heme-dependent enzyme, oxidoreductase
• 由来する生物種: Mycobacterium tuberculosis; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 163125.46

構造登録者

Liu, A.,Li, J. (登録日: 2024-02-19, 公開日: 2024-10-23, 最終更新日: 2025-01-08)

主引用文献

Li, J.,Duan, R.,Traore, E.S.,Nguyen, R.C.,Davis, I.,Griffth, W.P.,Goodwin, D.C.,Jarzecki, A.A.,Liu, A.
Indole N-Linked Hydroperoxyl Adduct of Protein-Derived Cofactor Modulating Catalase-Peroxidase Functions.
Angew.Chem.Int.Ed.Engl., 63:e202407018-e202407018, 2024

PubMed Abstract: Bifunctional catalase-peroxidase (KatG) features a posttranslational methionine-tyrosine-tryptophan (MYW) crosslinked cofactor crucial for its catalase function, enabling pathogens to neutralize hydrogen peroxide during infection. We discovered the presence of indole nitrogen-linked hydroperoxyl adduct (MYW-OOH) in Mycobacterium tuberculosis KatG in the solution state under ambient conditions, suggesting its natural occurrence. By isolating predominantly MYW-OOH-containing KatG protein, we investigated the chemical stability and functional impact of MYW-OOH. We discovered that MYW-OOH inhibits catalase activity, presenting a unique temporary lock. Exposure to peroxide or increased temperature removes the hydroperoxyl adduct from the protein cofactor, converting MYW-OOH to MYW and restoring the detoxifying ability of the enzyme against hydrogen peroxide. Thus, the N-linked hydroperoxyl group is releasable. KatG with MYW-OOH represents a catalase dormant, but primed, state of the enzyme. These findings provide insight into chemical strategies targeting the bifunctional enzyme KatG in pathogens, highlighting the role of N-linked hydroperoxyl modifications in enzymatic function.

PubMed: 39300819
DOI: 10.1002/anie.202407018

実験手法

X-RAY DIFFRACTION (2.35 Å)