A diferrous-dinitrosyl intermediate in the N2O-generating pathway of a deflavinated flavo-diiron protein

Biochemistry. 2014 Sep 9;53(35):5631-7. doi: 10.1021/bi500836z. Epub 2014 Aug 26.

Abstract

Flavo-diiron proteins (FDPs) function as anaerobic nitric oxide scavengers in some microorganisms, catalyzing reduction of nitric to nitrous oxide. The FDP from Thermotoga maritima can be prepared in a deflavinated form with an intact diferric site (deflavo-FDP). Hayashi et al. [(2010) Biochemistry 49, 7040-7049] reported that reaction of NO with reduced deflavo-FDP produced substoichiometric N2O. Here we report a multispectroscopic approach to identify the iron species in the reactions of deflavo-FDP with NO. Mössbauer spectroscopy identified two distinct ferrous species after reduction of the antiferromagnetically coupled diferric site. Approximately 60% of the total ferrous iron was assigned to a diferrous species associated with the N2O-generating pathway. This pathway proceeds through successive diferrous-mononitrosyl (S = (1)/2 Fe(II){FeNO}(7)) and diferrous-dinitrosyl (S = 0 [{FeNO}(7)]2) species that form within ∼100 ms of mixing of the reduced protein with NO. The diferrous-dinitrosyl intermediate converted to an antiferromagnetically coupled diferric species that was spectroscopically indistinguishable from that in the starting deflavinated protein. These diiron species closely resembled those reported for the flavinated FDP [Caranto et al. (2014) J. Am. Chem. Soc. 136, 7981-7992], and the time scales of their formation and decay were consistent with the steady state turnover of the flavinated protein. The remaining ∼40% of ferrous iron was inactive in N2O generation but reversibly bound NO to give an S = (3)/2 {FeNO}(7) species. The results demonstrate that N2O formation in FDPs can occur via conversion of S = 0 [{FeNO}(7)]2 to a diferric form without participation of the flavin cofactor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Electron Spin Resonance Spectroscopy
  • Flavoproteins / chemistry*
  • Flavoproteins / metabolism*
  • Iron / chemistry
  • Kinetics
  • Molecular Structure
  • Nitrous Oxide / metabolism*
  • Spectrophotometry
  • Spectroscopy, Mossbauer
  • Thermotoga maritima / chemistry
  • Thermotoga maritima / metabolism

Substances

  • Bacterial Proteins
  • Flavoproteins
  • Iron
  • Nitrous Oxide