title: The structure of Aquifex aeolicus sulfide:quinone oxidoreductase, a basis to understand sulfide detoxification and respiration.
abstract: Sulfide:quinone oxidoreductase (SQR) is a flavoprotein with homologues in all domains of life except plants. It plays a physiological role both in sulfide detoxification and in energy transduction. We isolated the protein from native membranes of the hyperthermophilic bacterium Aquifex aeolicus, and we determined its X-ray structure in the "as-purified," substrate-bound, and inhibitor-bound forms at resolutions of 2.3, 2.0, and 2.9 A, respectively. The structure is composed of 2 Rossmann domains and 1 attachment domain, with an overall monomeric architecture typical of disulfide oxidoreductase flavoproteins. A. aeolicus SQR is a surprisingly trimeric, periplasmic integral monotopic membrane protein that inserts about 12 A into the lipidic bilayer through an amphipathic helix-turn-helix tripodal motif. The quinone is located in a channel that extends from the si side of the FAD to the membrane. The quinone ring is sandwiched between the conserved amino acids Phe-385 and Ile-346, and it is possibly protonated upon reduction via Glu-318 and/or neighboring water molecules. Sulfide polymerization occurs on the re side of FAD, where the invariant Cys-156 and Cys-347 appear to be covalently bound to polysulfur fragments. The structure suggests that FAD is covalently linked to the polypeptide in an unusual way, via a disulfide bridge between the 8-methyl group and Cys-124. The applicability of this disulfide bridge for transferring electrons from sulfide to FAD, 2 mechanisms for sulfide polymerization and channeling of the substrate, S(2-), and of the product, S(n), in and out of the active site are discussed.
authors.affiliation: Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Max von Laue Strasse 3, D-60438 Frankfurt am Main, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Marcia
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ermler
authors.forename: Guohong
authors.initials: G
authors.lastname: Peng
authors.forename: Hartmut
authors.initials: H
authors.lastname: Michel
mesh_terms: D001419:Bacteria / Q000201:enzymology*; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D008658:Inactivation, Metabolic; D008958:Models, Molecular; D010100:Oxygen / Q000378:metabolism*; D011487:Protein Conformation; D011808:Quinone Reductases / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D013440:Sulfides / Q000378:metabolism*
chemical_list: D013440:Sulfides; D005182:Flavin-Adenine Dinucleotide; D011808:Quinone Reductases; C073412:sulfide quinone reductase; D010100:Oxygen