Evidence That the Pi Release Event Is the Rate-Limiting Step in the Nitrogenase Catalytic Cycle

Biochemistry. 2016 Jul 5;55(26):3625-35. doi: 10.1021/acs.biochem.6b00421. Epub 2016 Jun 22.

Abstract

Nitrogenase reduction of dinitrogen (N2) to ammonia (NH3) involves a sequence of events that occur upon the transient association of the reduced Fe protein containing two ATP molecules with the MoFe protein that includes electron transfer, ATP hydrolysis, Pi release, and dissociation of the oxidized, ADP-containing Fe protein from the reduced MoFe protein. Numerous kinetic studies using the nonphysiological electron donor dithionite have suggested that the rate-limiting step in this reaction cycle is the dissociation of the Fe protein from the MoFe protein. Here, we have established the rate constants for each of the key steps in the catalytic cycle using the physiological reductant flavodoxin protein in its hydroquinone state. The findings indicate that with this reductant, the rate-limiting step in the reaction cycle is not protein-protein dissociation or reduction of the oxidized Fe protein, but rather events associated with the Pi release step. Further, it is demonstrated that (i) Fe protein transfers only one electron to MoFe protein in each Fe protein cycle coupled with hydrolysis of two ATP molecules, (ii) the oxidized Fe protein is not reduced when bound to MoFe protein, and (iii) the Fe protein interacts with flavodoxin using the same binding interface that is used with the MoFe protein. These findings allow a revision of the rate-limiting step in the nitrogenase Fe protein cycle.

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Azotobacter vinelandii / metabolism*
  • Catalysis
  • Electron Transport
  • Hydrolysis
  • Molybdoferredoxin / chemistry
  • Molybdoferredoxin / metabolism*
  • Nitrogenase / chemistry
  • Nitrogenase / metabolism*
  • Oxidation-Reduction
  • Oxidoreductases / metabolism*
  • Protein Conformation

Substances

  • Molybdoferredoxin
  • Adenosine Triphosphate
  • Oxidoreductases
  • Nitrogenase
  • nitrogenase reductase