6WH6

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

Summary for 6WH6

• Entry DOI: 10.2210/pdb6wh6/pdb
• Descriptor: Sulfide:quinone oxidoreductase, mitochondrial, FLAVIN-ADENINE DINUCLEOTIDE, CYANIDE ION, ... (5 entities in total)
• Functional Keywords: oxidoreductase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 96385.86

Authors

Banerjee, R.,Cho, U.S.,Moon, S. (deposition date: 2020-04-07, release date: 2021-04-21, Last modification date: 2024-10-09)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.25 Å)