Abstract Details
| EXAFS Evidence of a High Valent Iron Intermediate in Enzymatic Halogenation Reactions | |
|---|---|
| Abstract ID | LCLS/SSRL-17a |
| Presenter | Pamela Riggs-Gelasco |
| Presentation Type | LCLS/SSRL Invited Speaker |
| Full Author List | Pamela Riggs-Gelasco (1) , Danica P. Galonic (2) , Eric W. Barr (3) , Megan L. Matthews (4) , Gretchen M. Koch (3) , J. Ryan Yonce (1) , J. Martin Bollinger, Jr. (3,4) , Christopher T. Walsh (2) , Carsten Krebs (3,4) |
| Affiliations | (1) Dept. of Chemistry and Biochemistry, College of Charleston (2) Dept. of Biological Chemistry and Molecular Pharmacology, Harvard Medical School (3) Dept. of Biochemistry and Molecular Biology, The Pennsylvania State University (4) Dept. of Chemistry, The Pennsylvania State University |
| Category | Bio/Life Sciences |
| Abstract | The enzyme CytC3 from Streptomyces halogenates the g-methyl group of L-aminobutyric acid to produce 4, 4-dichloroaminobutyric acid, an antibacterial amino acid, or 4-Cl-L-aminobutryric acid, the precursor of the aminocyclopropane moiety of cytotrienin. To achieve halogenation of the unactivated methyl carbon, CytC3 and other non-heme iron halogenases utilize a-ketoglutarate in an O2 dependent reaction to generate a high-valent Fe(IV)-oxo species. The intermediate abstracts a hydrogen atom from the substrate, allowing the incorporation of a metal-bound halide into the substrate radical.(1,2) We describe here the structural characterization of the CytC3 Fe(IV)-oxo intermediate that was generated in the presence of bromide rather than chloride using x-ray absorption and Mössbauer spectroscopies. Iron x-ray absorption spectroscopy demonstrates an Fe-Br interaction in the reactant CytC3:Fe(II):aKG:Br-:L-Aba-S-CytC2 complex of 2.51 Å. When this complex is reacted with oxygen for 2 s, a reaction intermediate is formed in high yield (80%). Mössbauer spectroscopy demonstrates that the novel species contains a high-spin Fe(IV) center. The enhanced preedge feature in the Fe-X-ray absorption spectra and the short Fe-oxygen and Fe-Br interactions of 1.62 A of 2.43 Å, respectively, support the formulation of this intermediate as a Br-Fe(IV)-oxo complex. |
| Footnotes | (1) For a recent review, see Vaillancourt, et al, Chem. Rev. 2006, 106, 3364-3378.
(2) Galonic, et al, Nature Chemical Biology 2006, 3, 113-116. |
| Funding Acknowledgement | |