title: Structure-function relationships in iron and manganese superoxide dismutases.
abstract: Using the complete sequences for MnSOD from Thermus thermophilus and for FeSOD from E. coli, structural models for both oxidized enzymes have been refined, the Mn protein to an R of 0.186 for all data between 10.0 and 1.8 A, and the Fe protein to an R of 0.22 for data between 10.0 and 2.5 A. The results of the refinements support the presence of a solvent as a fifth ligand to Mn(III) and Fe(III) and a coordination geometry that is close to trigonal bipyramidal. The putative substrate-entry channel is comprised of residues from both subunits of the dimer; several basic residues that are conserved may facilitate approach of O2-, while other conserved residues maintain interchain packing interactions. Analysis of the azide complex of Fe(III) dismutase suggests that during turnover O2- binds to the metal at a sixth coordination site without displacing the solvent ligand. Because crystals reduced with dithionite show no evidence for displacement of the protein ligands, the redox-linked proton acceptor (C. Bull and J.A. Fee (1985), Journal of the American Chemistry Society 107, 3295-3304) is unlikely to be one of the histidines which bind the metal ion. Structural, kinetic, titration, and spectroscopic data can be accommodated in a mechanistic scheme which accounts for the differential titration behaviour of the Fe(III) and Fe(II) enzymes at neutral and high pH.
authors.affiliation: Biophysics Research Division, University of Michigan.
authors.forename: W C
authors.initials: WC
authors.lastname: Stallings
authors.forename: A L
authors.initials: AL
authors.lastname: Metzger
authors.forename: K A
authors.initials: KA
authors.lastname: Pattridge
authors.forename: J A
authors.initials: JA
authors.lastname: Fee
authors.forename: M L
authors.initials: ML
authors.lastname: Ludwig
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D001665:Binding Sites; D004926:Escherichia coli / Q000201:enzymology; D007501:Iron; D008345:Manganese; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013824:Thermus / Q000201:enzymology
chemical_list: D001426:Bacterial Proteins; D008345:Manganese; D007501:Iron; D013482:Superoxide Dismutase