Crystal structure of the pristine peroxidase ferryl center and its relevance to proton-coupled electron transfer

Abstract

Fig. 1. Peroxidase mechanism. (A) Traditional "water-modified" mechanism of CmpI formation. In this mechanism, peroxide first coordinates with the heme iron, followed by proton transfer to the distal peroxide O atom via an ordered water molecule and the distal His. The protonation state of the distal His depends on the His pK a . Our computational experiments indicate that the pK a substantially increases in CmpI. (B) Modified mechanism based on the observation that His52 in CCP CmpI is protonated in the neutron diffraction structure (8). Going from the initial peroxide complex to CmpI proceeds via two possible routes, one of which involves the Fe(IV)-OH intermediate. (C) Mechanism of CmpII reduction, which includes a protoncoupled electron transfer event resulting in a net transfer of a proton from the distal His to the ferryl O atom.

Structure-Based Mechanism for Oxidative Decarboxylation Reactions Mediated by Amino Acids and Heme Propionates in Coproheme Decarboxylase (HemQ)

“…S1 and Results), 12 is completely absent in the coproheme decarboxylase. The coproheme is instead ligated by an uncharged proximal His (Fig 2–4) and its open coordination position is flanked by a distal Gln.…”

Metal-Assisted Oxo Atom Addition to an Fe(III) Thiolate

“…106–111 Hydrogen peroxide (H 2 O 2 ) has also been shown to convert Fe(III) compounds to Fe(V)═O species, 112, 113 or its redox equivalent. 107, 109, 111 In contrast to Fe(IV)═O compounds, 52, 98, 114–123 however, very few synthetic non-heme Fe(V)═O species have been observed. 93, 95, 96, 104, 113, 124 The most thoroughly characterized example, [Fe(V)(TAML)(O)] − , incorporates an electron-donating tetra-anionic carboxamide ligand ( vide inf ra ), TAML 4–93, 95, 104, 125, 126 .…”

Reactivity of an FeIV-Oxo Complex with Protons and Oxidants

“…9,10 Recent experimental findings have sparked discussions on whether protonation occurs at the Fe IV –oxo species or at a proximal site that then forms a H-bond to the oxido ligand. 11,12 The importance of protonated Fe IV –oxo species extends beyond heme proteins to non-heme systems that include the Rieske-type monooxygenases and synthetic systems, such as the one suggested by Fukusumi and Nam. 13,14 Unlike non-heme Fe IV –oxo species in which considerable progress has been made in understanding their properties, 15–20 there is a dearth of experimental evidence for protonated non-heme, Fe IV –oxo complexes.…”

“…10,21–23 Furthermore, most synthetic systems lack intramolecular H-bonding networks that are vital in regulating the site of protonation in proteins with Fe IV –oxo units. 11,12 …”

“…We argue these types of interactions are not limited to just our system and may occur within the active site of a protein or a synthetic complex, especially those with presumed high valent Fe–OH units. 11,12 For instance, mechanisms for non-heme iron enzymes and their synthetic models often invoke Fe IV –OH and Fe V –OH intermediates, 14,39–41 but evidence for the protonation of an Fe IV –oxo unit has only been observed in heme-containing proteins such as Compound II of P450s and the chloroperoxidases. 8,42,43 Such reactivity has yet to be definitively observed in other metalloproteins that invoke high valent Fe–OH species such as the Rieske non-heme oxygenases.…”