Structure of a Ferryl Mimic in the Archetypal Iron(II)- And 2-(Oxo)-glutarate-Dependent Dioxygenase, TauD

Katherine M. Davis, Madison Altmyer, Ryan J. Martinie, Irene Schaperdoth, Carsten Krebs, J. Martin Bollinger, Amie K. Boal

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Iron(II)- and 2-(oxo)-glutarate-dependent (Fe/2OG) oxygenases catalyze a diverse array of oxidation reactions via a common iron(IV)-oxo (ferryl) intermediate. Although the intermediate has been characterized spectroscopically, its short lifetime has precluded crystallograhic characterization. In solution, the ferryl was first observed directly in the archetypal Fe/2OG hydroxylase, taurine:2OG dioxygenase (TauD). Here, we substitute the iron cofactor of TauD with the stable vanadium(IV)-oxo (vanadyl) ion to obtain crystal structures mimicking the key ferryl complex. Intriguingly, whereas the structure of the TauD·(VIV-oxo)·succinate·taurine complex exhibits the expected orientation of the VO bond - trans to the His255 ligand and toward the C-H bond to be cleaved, in what has been termed the in-line configuration - the TauD·(VIV-oxo) binary complex is best modeled with its oxo ligand trans to Asp101. This off-line-like configuration is similar to one recently posited as a means to avoid hydroxylation in Fe/2OG enzymes that direct other outcomes, though neither has been visualized in an Fe/2OG structure to date. Whereas an off-line (trans to the proximal His) or off-line-like (trans to the carboxylate ligand) ferryl is unlikely to be important in the hydroxylation reaction of TauD, the observation that the ferryl may deviate from an in-line orientation in the absence of the primary substrate may explain the enzyme's mysterious self-hydroxylation behavior, should the oxo ligand lie trans to His99. This finding reinforces the potential for analogous functional off-line oxo configurations in halogenases, desaturases, and/or cyclases.

Original languageEnglish (US)
Pages (from-to)4218-4223
Number of pages6
JournalBiochemistry
Volume58
Issue number41
DOIs
StatePublished - Oct 15 2019

All Science Journal Classification (ASJC) codes

  • Biochemistry

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