Visualizing the reaction cycle in an Iron(II)- and 2-(Oxo)-glutarate-dependent hydroxylase

Andrew J. Mitchell, Noah P. Dunham, Ryan J. Martinie, Jonathan A. Bergman, Christopher J. Pollock, Kai Hu, Benjamin D. Allen, Wei Chen Chang, Alexey Silakov, Joseph M. Bollinger, Jr., Carsten Krebs, Amie Kathleen Boal

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Iron(II)- and 2-(oxo)-glutarate-dependent oxygenases catalyze diverse oxidative transformations that are often initiated by abstraction of hydrogen from carbon by iron(IV)-oxo (ferryl) complexes. Control of the relative orientation of the substrate C-H and ferryl Fe-O bonds, primarily by direction of the oxo group into one of two cisrelated coordination sites (termed inline and offline), may be generally important for control of the reaction outcome. Neither the ferryl complexes nor their fleeting precursors have been crystallographically characterized, hindering direct experimental validation of the offline hypothesis and elucidation of the means by which the protein might dictate an alternative oxo position. Comparison of high-resolution X-ray crystal structures of the substrate complex, an Fe(II)-peroxysuccinate ferryl precursor, and a vanadium(IV)-oxo mimic of the ferryl intermediate in the L-arginine 3-hydroxylase, VioC, reveals coordinated motions of active site residues that appear to control the intermediate geometries to determine reaction outcome.

Original languageEnglish (US)
Pages (from-to)13830-13836
Number of pages7
JournalJournal of the American Chemical Society
Volume139
Issue number39
DOIs
StatePublished - Jan 1 2017

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Glutarates
Oxygenases
Vanadium
Mixed Function Oxygenases
Arginine
Hydrogen
Catalytic Domain
Carbon
Iron
X-Rays
Proteins
Substrates
Crystal structure
X rays
Geometry
ferryl iron
Direction compound

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Mitchell, A. J., Dunham, N. P., Martinie, R. J., Bergman, J. A., Pollock, C. J., Hu, K., ... Boal, A. K. (2017). Visualizing the reaction cycle in an Iron(II)- and 2-(Oxo)-glutarate-dependent hydroxylase. Journal of the American Chemical Society, 139(39), 13830-13836. https://doi.org/10.1021/jacs.7b07374
Mitchell, Andrew J. ; Dunham, Noah P. ; Martinie, Ryan J. ; Bergman, Jonathan A. ; Pollock, Christopher J. ; Hu, Kai ; Allen, Benjamin D. ; Chang, Wei Chen ; Silakov, Alexey ; Bollinger, Jr., Joseph M. ; Krebs, Carsten ; Boal, Amie Kathleen. / Visualizing the reaction cycle in an Iron(II)- and 2-(Oxo)-glutarate-dependent hydroxylase. In: Journal of the American Chemical Society. 2017 ; Vol. 139, No. 39. pp. 13830-13836.
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Visualizing the reaction cycle in an Iron(II)- and 2-(Oxo)-glutarate-dependent hydroxylase. / Mitchell, Andrew J.; Dunham, Noah P.; Martinie, Ryan J.; Bergman, Jonathan A.; Pollock, Christopher J.; Hu, Kai; Allen, Benjamin D.; Chang, Wei Chen; Silakov, Alexey; Bollinger, Jr., Joseph M.; Krebs, Carsten; Boal, Amie Kathleen.

In: Journal of the American Chemical Society, Vol. 139, No. 39, 01.01.2017, p. 13830-13836.

Research output: Contribution to journalArticle

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