CD and MCD of CytC3 and taurine dioxygenase: Role of the facial triad in α-KG-dependent oxygenases

Michael L. Neidig, Christina D. Brown, Kenneth M. Light, Danica Galonić Fujimori, Elizabeth M. Nolan, John C. Price, Eric W. Barr, J. Martin Bollinger, Carsten Krebs, Christopher T. Walsh, Edward I. Solomon

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81 Scopus citations


The α-ketoglutarate (α-KG)-dependent oxygenases are a large and diverse class of mononuclear non-heme iron enzymes that require Fe II, α-KG, and dioxygen for catalysis with the α-KG cosubstrate supplying the additional reducing equivalents for oxygen activation. While these systems exhibit a diverse array of reactivities (i.e., hydroxylation, desaturation, ring closure, etc.), they all share a common structural motif at the FeII active site, termed the 2-His-1-carboxylate facial triad. Recently, a new subclass of α-KG-dependent oxygenases has been identified that exhibits novel reactivity, the oxidative halogenation of unactivated carbon centers. These enzymes are also structurally unique in that they do not contain the standard facial triad, as a Cl- ligand is coordinated in place of the carboxylate. An FeII methodology involving CD, MCD, and VTVH MCD spectroscopies was applied to CytC3 to elucidate the active-site structural effects of this perturbation of the coordination sphere. A significant decrease in the affinity of FeII for apo-CytC3 was observed, supporting the necessity of the facial triad for iron coordination to form the resting site. In addition, interesting differences observed in the FeII/α-KG complex relative to the cognate complex in other α-KG-dependent oxygenases indicate the presence of a distorted 6C site with a weak water ligand. Combined with parallel studies of taurine dioxygenase and past studies of clavaminate synthase, these results define a role of the carboxylate ligand of the facial triad in stabilizing water coordination via a H-bonding interaction between the noncoordinating oxygen of the carboxylate and the coordinated water. These studies provide initial insight into the active-site features that favor chlorination by CytC3 over the hydroxylation reactions occurring in related enzymes.

Original languageEnglish (US)
Pages (from-to)14224-14231
Number of pages8
JournalJournal of the American Chemical Society
Issue number46
StatePublished - Nov 21 2007

All Science Journal Classification (ASJC) codes

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


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