6edh
Taurine:2OG dioxygenase (TauD) bound to the vanadyl ion, taurine, and succinate
Structural highlights
FunctionTAUD_ECOLI Catalyzes the conversion of taurine and alpha ketoglutarate to sulfite, aminoacetaldehyde and succinate. Required for the utilization of taurine (2-aminoethanesulfonic acid) as an alternative sulfur source. Pentane-sulfonic acid, 3-(N-morpholino)propanesulfonic acid and 1,3-dioxo-2-isoindolineethanesulfonic acid are also substrates for this enzyme. Publication Abstract from PubMedIron(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.(V(IV)-oxo).succinate.taurine complex exhibits the expected orientation of the V identical withO 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.(V(IV)-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. Structure of a Ferryl Mimic in the Archetypal Iron(II)- and 2-(Oxo)-glutarate-Dependent Dioxygenase, TauD.,Davis KM, Altmyer M, Martinie RJ, Schaperdoth I, Krebs C, Bollinger JM Jr, Boal AK Biochemistry. 2019 Oct 15;58(41):4218-4223. doi: 10.1021/acs.biochem.9b00598., Epub 2019 Oct 2. PMID:31503454[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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