title: Investigation of ion binding in chlorite dismutases by means of molecular dynamics simulations.
abstract: Chlorite dismutases are prokaryotic heme b oxidoreductases that convert chlorite to chloride and dioxygen. It has been postulated that during turnover hypochlorite is formed transiently, which might be responsible for the observed irreversible inactivation of these iron proteins. The only charged distal residue in the heme cavity is a conserved and mobile arginine, but its role in catalysis and inactivation is not fully understood. In the present study, the pentameric chlorite dismutase (Cld) from the bacterium Candidatus Nitrospira defluvii was probed for binding of the low spin ligand cyanide, the substrate chlorite, and the intermediate hypochlorite. Simulations were performed with the enzyme in the ferrous, ferric, and compound I state. Additionally, the variant R173A was studied. We report the parametrization for the GROMOS force field of the anions ClO(-), ClO2(-), ClO3(-), and ClO4(-) and describe spontaneous binding, unbinding, and rebinding events of chlorite and hypochlorite, as well as the dynamics of the conformations of Arg173 during simulations. The findings suggest that (i) chlorite binding to ferric NdCld occurs spontaneously and (ii) that Arg173 is important for recognition and to impair hypochlorite leakage from the reaction sphere. The simulation data is discussed in comparison with experimental data on catalysis and inhibition of chlorite dismutase.
authors.affiliation: Department of Material Sciences and Process Engineering, Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences Vienna , Muthgasse 18, A-1190 Vienna, Austria.
authors.forename: Axel
authors.initials: A
authors.lastname: Sündermann
authors.forename: Maria M
authors.initials: MM
authors.lastname: Reif
authors.forename: Stefan
authors.initials: S
authors.lastname: Hofbauer
authors.forename: Christian
authors.initials: C
authors.lastname: Obinger
authors.forename: Chris
authors.initials: C
authors.lastname: Oostenbrink
mesh_terms: D000838:Anions; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D002412:Cations; D002712:Chlorides / Q000737:chemistry; D003486:Cyanides / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry; D005296:Ferrous Compounds / Q000737:chemistry; D006997:Hypochlorous Acid / Q000737:chemistry; D007501:Iron / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009154:Mutation; D010088:Oxidoreductases / Q000737:chemistry* / Q000235:genetics; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization
chemical_list: D000838:Anions; D001426:Bacterial Proteins; D002412:Cations; D002712:Chlorides; D003486:Cyanides; D005290:Ferric Compounds; D005296:Ferrous Compounds; D006997:Hypochlorous Acid; D007501:Iron; D010088:Oxidoreductases; C402794:chlorite dismutase; C001599:chlorite