Journal article
X-Ray Structure of Human Sulfide:Quinone Oxidoreductase: Insights into the Mechanism of Mitochondrial Hydrogen Sulfide Oxidation
Structure (London), v 27(5), pp 794-805.e4
07 May 2019
PMID: 30905673
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Hydrogen sulfide (H2S) 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 H2S. 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 H2S-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.
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Details
- Title
- X-Ray Structure of Human Sulfide:Quinone Oxidoreductase: Insights into the Mechanism of Mitochondrial Hydrogen Sulfide Oxidation
- Creators
- Michael R. Jackson - Drexel UniversityPatrick J. Loll - Drexel UniversityMarilyn Schuman Joms - Drexel Univ, Coll Med, Biochem & Mol Biol, 245 N 15th St, Philadelphia, PA 19102 USAArgonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Publication Details
- Structure (London), v 27(5), pp 794-805.e4
- Publisher
- Elsevier
- Number of pages
- 16
- Grant note
- R01 GM107389 / National Institutes of Health General Medical Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) DE-AC02-06CH11357 / DOE Office of Science; United States Department of Energy (DOE) P41GM103403 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) R41 HL134435 / NIH National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) P41 GM103403 / National Institute of General Medical Sciences from the NIH R41HL134435 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) S10 RR029205 / NIH-ORIP HEI grant
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; [Retired Faculty]
- Web of Science ID
- WOS:000467238900009
- Scopus ID
- 2-s2.0-85064946050
- Other Identifier
- 991019169518604721
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- Web of Science research areas
- Biochemistry & Molecular Biology
- Biophysics
- Cell Biology