Dioxygen activation by nonheme iron enzymes with the 2-His-1-carboxylate facial triad that generate high-valent oxoiron oxidants

Abstract

The 2-His-1-carboxylate facial triad is a widely used scaffold to bind the iron center in mononuclear nonheme iron enzymes for activating dioxygen in a variety of oxidative transformations of metabolic significance. Since the 1990s, over a hundred different iron enzymes have been identified to use this platform. This structural motif consists of two histidines and the side chain carboxylate of an aspartate or a glutamate arranged in a facial array that binds iron(II) at the active site. This triad occupies one face of an iron-centered octahedron and makes the opposite face available for the coordination of O and, in many cases, substrate, allowing the tailoring of the iron-dioxygen chemistry to carry out a plethora of diverse reactions. Activated dioxygen-derived species involved in the enzyme mechanisms include iron(III)-superoxo, iron(III)-peroxo, and high-valent iron(IV)-oxo intermediates. In this article, we highlight the major crystallographic, spectroscopic, and mechanistic advances of the past 20 years that have significantly enhanced our understanding of the mechanisms of O activation and the key roles played by iron-based oxidants.

Equilibrating (L)FeIII–OOAc and (L)FeV(O) Species in Hydrocarbon Oxidations by Bio-Inspired Nonheme Iron Catalysts Using H2O2 and AcOH

“…1–3 Among these biological catalysts, a particularly broad and versatile class activates dioxygen at an iron center ligated by a common 2-histidine-1-carboxylate facial triad motif. 3–6 One of the more intriguing members of this class is the Rieske oxygenase family of enzymes, which requires two electrons from NADH to activate dioxygen and carry out a wide array of important transformations, including C–H and C=C bond oxygenation, O - and N -demethylation, and C–C bond formation. 5, 7 For naphthalene 1,2-dioxygenase and carbazole 1,9a-dioxygenase, O 2 adducts of the respective enzyme-substrate complexes have been trapped in crystals and found to possess a dioxygen unit that is side-on bound to the iron center and in close proximity to the target C=C bond of the bound substrate.…”

Crystal structures reveal metal-binding plasticity at the metallo-β-lactamase active site of PqqB from Pseudomonas putida

“…Taken together, these data are consistent with a mono-metal binding capability for PqqB, as observed in our crystal structures. The juxtaposition of Asp92, His93, and His269 in PpPqqB is reminiscent of a 2-His/1-carboxylate facial triad, the characteristic binding motif of nonheme iron oxygenases [13]. Therefore, it was highly surprising when attempts to bind iron in the canonical MBL active site failed.…”

“…S1). However, PqqB does retain the potential for a single metal binding site equivalent to one in PhnP, a 2-His/1-carboxylate facial triad that is characteristic of nonheme iron oxygenases, although PhnP has an additional ligand, Asp164, that bridges between the two Mn 2+ sites that is absent in PqqB [13]. Structural comparison between the previously determined 2.2 Å resolution structure of Pseudomonas putida PqqB (PpPqqB) that had no metal in the canonical MBL active site, and the 1.4 Å resolution structure of di-Mn 2+ -bound PhnP further demonstrates this loss (Fig.…”

Oxygen activation by mononuclear nonheme iron dioxygenases involved in the degradation of aromatics

“…However, in the latter two cases, only one atom of O 2 is incorporated into the primary organic substrate, while the other O-atom ends up on the organic cosubstrate, which provides two of the four electrons needed for oxygen reduction. These latter types of mononuclear nonheme Fe dioxygenases are discussed elsewhere in this special issue [7]. …”