Trapping and spectroscopic characterization of an FeIII-superoxo intermediate from a nonheme mononuclear iron-containing enzyme

Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16788-93. doi: 10.1073/pnas.1010015107. Epub 2010 Sep 13.

Abstract

Fe(III)-O(2)*(-) intermediates are well known in heme enzymes, but none have been characterized in the nonheme mononuclear Fe(II) enzyme family. Many steps in the O(2) activation and reaction cycle of Fe(II)-containing homoprotocatechuate 2,3-dioxygenase are made detectable by using the alternative substrate 4-nitrocatechol (4NC) and mutation of the active site His200 to Asn (H200N). Here, the first intermediate (Int-1) observed after adding O(2) to the H200N-4NC complex is trapped and characterized using EPR and Mössbauer (MB) spectroscopies. Int-1 is a high-spin (S(1) = 5/2) Fe(III) antiferromagnetically (AF) coupled to an S(2) = 1/2 radical (J ≈ 6 cm(-1) in ). It exhibits parallel-mode EPR signals at g = 8.17 from the S = 2 multiplet, and g = 8.8 and 11.6 from the S = 3 multiplet. These signals are broadened significantly by hyperfine interactions (A((17)O) ≈ 180 MHz). Thus, Int-1 is an AF-coupled species. The experimental observations are supported by density functional theory calculations that show nearly complete transfer of spin density to the bound O(2). Int-1 decays to form a second intermediate (Int-2). MB spectra show that it is also an AF-coupled Fe(III)-radical complex. Int-2 exhibits an EPR signal at g = 8.05 arising from an S = 2 state. The signal is only slightly broadened by (< 3% spin delocalization), suggesting that Int-2 is a peroxo-Fe(III)-4NC semiquinone radical species. Our results demonstrate facile electron transfer between Fe(II), O(2), and the organic ligand, thereby supporting the proposed wild-type enzyme mechanism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Catechols / chemistry*
  • Crystallography
  • Dioxygenases / chemistry*
  • Dioxygenases / genetics
  • Electron Spin Resonance Spectroscopy
  • Electron Transport
  • Iron / chemistry*
  • Mutation
  • Nitro Compounds / chemistry*
  • Oxidation-Reduction
  • Spectroscopy, Mossbauer
  • Substrate Specificity
  • Superoxides / chemistry*

Substances

  • Catechols
  • Nitro Compounds
  • nitrocatechol
  • Superoxides
  • Iron
  • Dioxygenases
  • 3,4-dihydroxyphenylacetate 2,3-dioxygenase