title: Isomorphic deactivation of a Pseudomonas aeruginosa oxidoreductase: The crystal structure of Ag(I) metallated azurin at 1.7 Å.
abstract: Multiple biophysical methods demonstrate that silver effectively metallates Pseudomonas aeruginosa apo-azurin in solution. X-ray crystallography of the silver-modified protein reveals that silver binds to azurin at the traditional copper mediated active site with nearly identical geometry. Cyclic voltammetry indicates that the silver adduct is redox inert. Our results suggest that a potential mechanism for the microbial toxicity of silver is the deactivation of copper oxidoreductases by the effective binding and structural mimicry by silver without the corresponding function.
authors.affiliation: Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA; Center for Silver Therapeutics Research, The University of Akron, Akron, OH 44325-3601, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Panzner
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Bilinovich
authors.forename: Jillian A
authors.initials: JA
authors.lastname: Parker
authors.forename: Erika L
authors.initials: EL
authors.lastname: Bladholm
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ziegler
authors.forename: Steven M
authors.initials: SM
authors.lastname: Berry
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Leeper
mesh_terms: D001400:Azurin / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D003300:Copper / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D004789:Enzyme Activation / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010084:Oxidation-Reduction / Q000187:drug effects; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D012834:Silver / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D001400:Azurin; D012834:Silver; D003300:Copper; D010088:Oxidoreductases
keywords: Azurin; Crystallography; NMR; Silver ion