title: Structure of adenylylsulfate reductase from the hyperthermophilic Archaeoglobus fulgidus at 1.6-A resolution.
abstract: The iron-sulfur flavoenzyme adenylylsulfate (adenosine 5'-phosphosulfate, APS) reductase catalyzes reversibly the reduction of APS to sulfite and AMP. The structures of APS reductase from the hyperthermophilic Archaeoglobus fulgidus in the two-electron reduced state and with sulfite bound to FAD are reported at 1.6- and 2.5- resolution, respectively. The FAD-sulfite adduct was detected after soaking the crystals with APS. This finding and the architecture of the active site strongly suggest that catalysis involves a nucleophilic attack of the N5 atom of reduced FAD on the sulfur atom of APS. In view of the high degree of similarity between APS reductase and fumarate reductase especially with regard to the FAD-binding alpha-subunit, it is proposed that both subunits originate from a common ancestor resembling archaeal APS reductase. The two electrons required for APS reduction are transferred via two [4Fe-4S] clusters from the surface of the protein to FAD. The exceptionally large difference in reduction potential of these clusters (-60 and -500 mV) can be explained by interactions of the clusters with the protein matrix.
authors.affiliation: Fachbereich Biologie, Mathematisch-Naturwissenschaftliche Sektion, Universität Konstanz, Fach M665, D-78457 Konstanz, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Fritz
authors.forename: Annette
authors.initials: A
authors.lastname: Roth
authors.forename: Alexander
authors.initials: A
authors.lastname: Schiffer
authors.forename: Thomas
authors.initials: T
authors.lastname: Büchert
authors.forename: Gleb
authors.initials: G
authors.lastname: Bourenkov
authors.forename: Hans D
authors.initials: HD
authors.lastname: Bartunik
authors.forename: Harald
authors.initials: H
authors.lastname: Huber
authors.forename: Karl O
authors.initials: KO
authors.lastname: Stetter
authors.forename: Peter M H
authors.initials: PM
authors.lastname: Kroneck
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ermler
mesh_terms: D019611:Archaeoglobus fulgidus / Q000201:enzymology*; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D004578:Electron Spin Resonance Spectroscopy; D004583:Electrons; D005420:Flavoproteins / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D005420:Flavoproteins; D010088:Oxidoreductases; D013385:Succinate Dehydrogenase; D050862:Oxidoreductases Acting on Sulfur Group Donors; C019618:adenylylsulfate reductase