The 2-His-1-carboxylate facial triad: a versatile platform for dioxygen activation by mononuclear non-heme iron(II) enzymes

Abstract

General knowledge of dioxygen-activating mononuclear non-heme iron(II) enzymes containing a 2-His-1-carboxylate facial triad has significantly expanded in the last few years, due in large part to the extensive library of crystal structures that is now available. The common structural motif utilized by this enzyme superfamily acts as a platform upon which a wide assortment of substrate transformations are catalyzed. The facial triad binds a divalent metal ion at the active site, which leaves the opposite face of the octahedron available to coordinate a variety of exogenous ligands. The binding of substrate activates the metal center for attack by dioxygen, which is subsequently converted to a high-valent iron intermediate, a formidable oxidizing species. Herein, we summarize crystallographic and mechanistic features of this metalloenzyme superfamily, which has enabled the proposal of a common but flexible pathway for dioxygen activation.

SyrB2 in syringomycin E biosynthesis is a nonheme Fe II α-ketoglutarate- and O 2 -dependent halogenase

“…2A). The holo form (phosphopantetheinylated) of the T domain was generated posttranslationally in situ through action of Sfp (20) and aspartate as putative ligands for Fe II (26)(27). The formation of the Fe IV AO ferryl species is likely to be a common intermediate in both the oxygenase and halogenase mechanism.…”

Mitochondrial regulation of epigenetics and its role in human diseases

“…2A). The JmjCdomain proteins (JMJD), another family of histone demethylases, use α-KG and iron (Fe) as co-factors 77 to demethylate the repressive H3K27me3/2 76,78 (Fig. 2B).…”

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“…16 Isopenicillin N synthase is a member of a family of mononuclear non-heme iron enzymes with a 2-His-1-carboxylate iron-binding motif. [17][18][19] It uses the four-electron oxidative power of 21 ferrous iron, which gives a ferric superoxo species 22 that activates the cysteine β-C-H bond leading to formation of an iron-bound peroxide. 23 According to the proposal in reference 20, the peroxide abstracts the valine N-H proton to generate the ferryl-oxo and a water molecule.…”