6WH6

Crystal structure of human sulfide quinone oxidoreductase in complex with coenzyme Q (cyanide soaked)

6WH6 の概要

• エントリーDOI: 10.2210/pdb6wh6/pdb
• 分子名称: Sulfide:quinone oxidoreductase, mitochondrial, FLAVIN-ADENINE DINUCLEOTIDE, CYANIDE ION, ... (5 entities in total)
• 機能のキーワード: oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 96385.86

構造登録者

Banerjee, R.,Cho, U.S.,Moon, S. (登録日: 2020-04-07, 公開日: 2021-04-21, 最終更新日: 2024-10-09)

主引用文献

Landry, A.P.,Moon, S.,Bonanata, J.,Cho, U.S.,Coitino, E.L.,Banerjee, R.
Dismantling and Rebuilding the Trisulfide Cofactor Demonstrates Its Essential Role in Human Sulfide Quinone Oxidoreductase.
J.Am.Chem.Soc., 142:14295-14306, 2020

PubMed Abstract: Sulfide quinone oxidoreductase (SQOR) catalyzes the first step in sulfide clearance, coupling HS oxidation to coenzyme Q reduction. Recent structures of human SQOR revealed a sulfur atom bridging the SQOR active site cysteines in a trisulfide configuration. Here, we assessed the importance of this cofactor using kinetic, crystallographic, and computational modeling approaches. Cyanolysis of SQOR proceeds via formation of an intense charge transfer complex that subsequently decays to eliminate thiocyanate. We captured a disulfanyl-methanimido thioate intermediate in the SQOR crystal structure, revealing how cyanolysis leads to reversible loss of SQOR activity that is restored in the presence of sulfide. Computational modeling and MD simulations revealed an ∼10-fold rate enhancement for nucleophilic addition of sulfide into the trisulfide versus a disulfide cofactor. The cysteine trisulfide in SQOR is thus critical for activity and provides a significant catalytic advantage over a cysteine disulfide.

PubMed: 32787249
DOI: 10.1021/jacs.0c06066

実験手法

X-RAY DIFFRACTION (2.25 Å)