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, J. Martin Bollinger, Carsten Krebs, Amie K. Boal

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


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
Issue number39
StatePublished - Oct 4 2017

All Science Journal Classification (ASJC) codes

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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