Isocyanides inhibit [Fe]-hydrogenase with very high affinity

FEBS Lett. 2011 Jan 21;585(2):353-6. doi: 10.1016/j.febslet.2010.12.014. Epub 2010 Dec 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / antagonists & inhibitors*
  • Binding Sites
  • Catalysis
  • Cyanides / pharmacology*
  • Enzyme Inhibitors
  • Hydrogenase / antagonists & inhibitors*
  • Iron-Sulfur Proteins / antagonists & inhibitors*
  • Kinetics
  • Methanobacteriaceae / enzymology
  • Protein Conformation / drug effects
  • Spectrum Analysis

Substances

  • Bacterial Proteins
  • Cyanides
  • Enzyme Inhibitors
  • Iron-Sulfur Proteins
  • iron hydrogenase
  • Hydrogenase