6MP5

Crystal structure of native human sulfide:quinone oxidoreductase

Summary for 6MP5

• Entry DOI: 10.2210/pdb6mp5/pdb
• Descriptor: Sulfide:quinone oxidoreductase, mitochondrial, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: sulfide:quinone oxidoreductase, rossman fold, hydrogen sulfide metabolism, thiocystine, membrane protein, oxidoreductase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 188403.03

Authors

Jackson, M.R.,Jorns, M.S.,Loll, P.J. (deposition date: 2018-10-05, release date: 2019-04-10, Last modification date: 2024-10-16)

Primary citation

Jackson, M.R.,Loll, P.J.,Jorns, M.S.
X-Ray Structure of Human Sulfide:Quinone Oxidoreductase: Insights into the Mechanism of Mitochondrial Hydrogen Sulfide Oxidation.
Structure, 27:794-805.e4, 2019

PubMed Abstract: Hydrogen sulfide (HS) is a gasotransmitter exhibiting pivotal functions in diverse biological processes, including activation of multiple cardioprotective pathways. Sulfide:quinone oxidoreductase (SQOR) is an integral membrane flavoprotein that catalyzes the first step in the mitochondrial metabolism of HS. As such, it plays a critical role in controlling physiological levels of the gasotransmitter and has attracted keen interest as a potential drug target. We report the crystal structure of human SQOR, unraveling the molecular basis for the enzyme's ability to catalyze sulfane sulfur transfer reactions with structurally diverse acceptors. We demonstrate that human SQOR contains unique features: an electropositive surface depression implicated as a binding site for sulfane sulfur acceptors and postulated to funnel negatively charged substrates to a hydrophilic HS-oxidizing active site, which is connected to a hydrophobic internal tunnel that binds coenzyme Q. These findings support a proposed model for catalysis and open the door for structure-based drug design.

PubMed: 30905673
DOI: 10.1016/j.str.2019.03.002

Experimental method

X-RAY DIFFRACTION (2.99 Å)