X-Ray Structure of Human Sulfide:Quinone Oxidoreductase: Insights into the Mechanism of Mitochondrial Hydrogen Sulfide Oxidation.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Author(s): Jackson MR;Jackson MR; Loll PJ; Loll PJ; Jorns MS; Jorns MS
  • Source:
    Structure (London, England : 1993) [Structure] 2019 May 07; Vol. 27 (5), pp. 794-805.e4. Date of Electronic Publication: 2019 Mar 21.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Cell Press Country of Publication: United States NLM ID: 101087697 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-4186 (Electronic) Linking ISSN: 09692126 NLM ISO Abbreviation: Structure Subsets: MEDLINE
    • Publication Information:
      Publication: 2000- : Cambridge, Mass. : Cell Press
      Original Publication: London : Current Biology, c1993-
    • Subject Terms:
      Hydrogen Sulfide/*chemistry ; Mitochondria/*metabolism ; Oxidoreductases Acting on Sulfur Group Donors/*chemistry ; Oxygen/*chemistry; Binding Sites ; Catalytic Domain ; Crystallography, X-Ray ; Cysteine/analogs & derivatives ; Cysteine/chemistry ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Oxidation-Reduction ; Protein Binding ; Protein Domains ; Protein Structure, Quaternary
    • Abstract:
      Hydrogen sulfide (H 2 S) 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 H 2 S. 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 H 2 S-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.
      (Copyright © 2019 Elsevier Ltd. All rights reserved.)
    • References:
      Appl Environ Microbiol. 2017 Oct 31;83(22):. (PMID: 28864655)
      J Mol Biol. 2010 Apr 30;398(2):292-305. (PMID: 20303979)
      J Biol Chem. 2015 Oct 9;290(41):25072-80. (PMID: 26318450)
      Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1617-32. (PMID: 23897484)
      Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21. (PMID: 20057044)
      Methods Mol Biol. 2007;363:91-108. (PMID: 17272838)
      Biochemistry. 2012 Aug 28;51(34):6804-15. (PMID: 22852582)
      Nat Protoc. 2008;3(11):1782-95. (PMID: 18974737)
      Methods Mol Biol. 2008;426:419-35. (PMID: 18542881)
      Nature. 1992 Jan 30;355(6359):472-5. (PMID: 18481394)
      Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21. (PMID: 20124702)
      J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674. (PMID: 19461840)
      Protein Expr Purif. 2005 May;41(1):207-34. (PMID: 15915565)
      Bioinformatics. 2008 Sep 15;24(18):2101-2. (PMID: 18662927)
      Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42. (PMID: 21460441)
      J Biol Chem. 2014 Nov 7;289(45):30901-10. (PMID: 25225291)
      Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):282-92. (PMID: 21460446)
      Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2184-95. (PMID: 15572771)
      Circulation. 2013 Jun 25;127(25):2523-34. (PMID: 23704252)
      Biochemistry. 2012 Aug 21;51(33):6556-67. (PMID: 22827326)
      Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9625-30. (PMID: 19487671)
      J Mol Biol. 2007 Sep 21;372(3):774-97. (PMID: 17681537)
      Acta Crystallogr D Struct Biol. 2017 Feb 1;73(Pt 2):148-157. (PMID: 28177311)
      Proteins. 2010 Apr;78(5):1073-83. (PMID: 20077566)
      Biochemistry. 2017 Feb 21;56(7):986-996. (PMID: 28107627)
      Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):352-67. (PMID: 22505256)
      Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32. (PMID: 15572765)
      Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):271-81. (PMID: 21460445)
      Biochemistry. 2009 Jun 23;48(24):5613-22. (PMID: 19438211)
      Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14. (PMID: 23793146)
      Nucleic Acids Res. 2012 Jan;40(Database issue):D370-6. (PMID: 21890895)
      Am J Physiol Heart Circ Physiol. 2016 Apr 1;310(7):H802-12. (PMID: 26801305)
      J Cheminform. 2009 Sep 11;1:15. (PMID: 20150996)
      Nucleic Acids Res. 2015 Jul 1;43(W1):W314-9. (PMID: 25908787)
      Science. 2008 Oct 24;322(5901):587-90. (PMID: 18948540)
      Acta Crystallogr D Struct Biol. 2018 Jul 1;74(Pt 7):632-642. (PMID: 29968673)
      Science. 1994 Oct 21;266(5184):430-2. (PMID: 7939681)
      Acta Crystallogr A. 2008 Jan;64(Pt 1):112-22. (PMID: 18156677)
      Acta Crystallogr D Biol Crystallogr. 1999 Oct;55(Pt 10):1703-17. (PMID: 10531520)
      Annu Rev Pharmacol Toxicol. 2011;51:169-87. (PMID: 21210746)
    • Grant Information:
      P41 GM103403 United States GM NIGMS NIH HHS; R01 GM107389 United States GM NIGMS NIH HHS; R41 HL134435 United States HL NHLBI NIH HHS; S10 RR029205 United States RR NCRR NIH HHS
    • Contributed Indexing:
      Keywords: X-ray crystallography; flavoprotein disulfide reductase family; human integral membrane protein; hydrogen sulfide metabolism; thiocystine
    • Accession Number:
      5652-32-4 (thiocysteine)
      EC 1.8.- (Oxidoreductases Acting on Sulfur Group Donors)
      EC 1.8.5.- (SQOR protein, human)
      K848JZ4886 (Cysteine)
      S88TT14065 (Oxygen)
      YY9FVM7NSN (Hydrogen Sulfide)
    • Publication Date:
      Date Created: 20190326 Date Completed: 20200608 Latest Revision: 20200608
    • Publication Date:
      20221213
    • Accession Number:
      PMC6724705
    • Accession Number:
      10.1016/j.str.2019.03.002
    • Accession Number:
      30905673