Equilibrium and ultrafast kinetic studies manipulating electron transfer: A short-lived flavin semiquinone is not sufficient for electron bifurcation

J Biol Chem. 2017 Aug 25;292(34):14039-14049. doi: 10.1074/jbc.M117.794214. Epub 2017 Jun 14.

Abstract

Flavin-based electron transfer bifurcation is emerging as a fundamental and powerful mechanism for conservation and deployment of electrochemical energy in enzymatic systems. In this process, a pair of electrons is acquired at intermediate reduction potential (i.e. intermediate reducing power), and each electron is passed to a different acceptor, one with lower and the other with higher reducing power, leading to "bifurcation." It is believed that a strongly reducing semiquinone species is essential for this process, and it is expected that this species should be kinetically short-lived. We now demonstrate that the presence of a short-lived anionic flavin semiquinone (ASQ) is not sufficient to infer the existence of bifurcating activity, although such a species may be necessary for the process. We have used transient absorption spectroscopy to compare the rates and mechanisms of decay of ASQ generated photochemically in bifurcating NADH-dependent ferredoxin-NADP+ oxidoreductase and the non-bifurcating flavoproteins nitroreductase, NADH oxidase, and flavodoxin. We found that different mechanisms dominate ASQ decay in the different protein environments, producing lifetimes ranging over 2 orders of magnitude. Capacity for electron transfer among redox cofactors versus charge recombination with nearby donors can explain the range of ASQ lifetimes that we observe. Our results support a model wherein efficient electron propagation can explain the short lifetime of the ASQ of bifurcating NADH-dependent ferredoxin-NADP+ oxidoreductase I and can be an indication of capacity for electron bifurcation.

Keywords: electron bifurcation; electron transfer; energetics; flavin; flavoprotein; fluorescence; transient absorption spectroscopy.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Apoenzymes / chemistry
  • Apoenzymes / genetics
  • Apoenzymes / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Benzoic Acid / chemistry
  • Benzoic Acid / metabolism
  • Biocatalysis
  • Desulfovibrio vulgaris / enzymology
  • Electron Transport
  • Enterobacter cloacae / enzymology
  • Flavin-Adenine Dinucleotide / analogs & derivatives*
  • Flavin-Adenine Dinucleotide / chemistry
  • Flavin-Adenine Dinucleotide / metabolism
  • Flavodoxin / chemistry
  • Flavodoxin / genetics
  • Flavodoxin / metabolism*
  • Holoenzymes / chemistry
  • Holoenzymes / genetics
  • Holoenzymes / metabolism
  • Models, Molecular*
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • NADH, NADPH Oxidoreductases / chemistry
  • NADH, NADPH Oxidoreductases / genetics
  • NADH, NADPH Oxidoreductases / metabolism*
  • Nitroreductases / chemistry
  • Nitroreductases / genetics
  • Nitroreductases / metabolism*
  • Oxidation-Reduction
  • Oxidoreductases / chemistry
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Pyrococcus furiosus / enzymology
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Silent Mutation
  • Thermus thermophilus / enzymology
  • ortho-Aminobenzoates / chemistry
  • ortho-Aminobenzoates / metabolism

Substances

  • Apoenzymes
  • Bacterial Proteins
  • Flavodoxin
  • Holoenzymes
  • Multienzyme Complexes
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • ortho-Aminobenzoates
  • anthranilic acid
  • Flavin-Adenine Dinucleotide
  • flavin semiquinone
  • Benzoic Acid
  • fenamic acid
  • Oxidoreductases
  • ferredoxin-NAD+ reductase
  • NADH oxidase
  • NADH, NADPH Oxidoreductases
  • Nitroreductases

Associated data

  • PDB/1NOX.pdb
  • PDB/1KQC.pdb
  • PDB/5JFC.pdb
  • PDB/1J8Q.pdb