title: Isocyanides inhibit [Fe]-hydrogenase with very high affinity.
abstract: [Fe]-Hydrogenase catalyzes the reversible activation of H(2). CO and CN(-) inhibit this enzyme with low affinity (K(i)≅0.1 mM) by binding to the iron site of the bound iron-guanyrylpyridinol cofactor. We report here that isocyanides, which are formally isoelectronic with CO and CN(-), strongly inhibit [Fe]-hydrogenase (K(i) as low as 1 nM). The [NiFe]- and [FeFe]-hydrogenases tested were not inhibited by isocyanides. UV-Vis and infrared spectra revealed that the isocyanides bind to the iron center of [Fe]-hydrogenase. The inhibition kinetics are in agreement with the proposed catalytic mechanism, including the open/closed conformational change of the enzyme.
authors.affiliation: Max-Planck-Institut für terrestrische Mikrobiologie, Marburg, Germany. shima@mpi-marburg.mpg.de
authors.forename: Seigo
authors.initials: S
authors.lastname: Shima
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ataka
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D001665:Binding Sites; D002384:Catalysis; D003486:Cyanides / Q000494:pharmacology*; D004791:Enzyme Inhibitors; D006864:Hydrogenase / Q000037:antagonists & inhibitors*; D007506:Iron-Sulfur Proteins / Q000037:antagonists & inhibitors*; D007700:Kinetics; D017013:Methanobacteriaceae / Q000201:enzymology; D011487:Protein Conformation / Q000187:drug effects; D013057:Spectrum Analysis
chemical_list: D001426:Bacterial Proteins; D003486:Cyanides; D004791:Enzyme Inhibitors; D007506:Iron-Sulfur Proteins; C118830:iron hydrogenase; D006864:Hydrogenase