Freundschaft

Wiertz, Svenja

doi:10.1515/9783110703238

Cited by 4 publications

(1 citation statement)

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“…21 Presenting a fourth possibility, our recent investigation into reactivity in a synthetic model (employing a Fe-O-O-Cu complex and an exogenous phenol) showed experimentally that PT can occur after the barrier and late in O-O cleavage. 10 Although direct evidence has remained elusive, the fourth erequired for O 2 reduction is generally considered to come from Tyr244 (although some reports 22,23 have suggested other protein residues). Since oxidation of a protonated Tyr would be thermodynamically uphill, the timing of ET can be loosely defined as after the Tyr is deprotonated.…”

Section: Introductionmentioning

confidence: 99%

Geometric and Electronic Structure Contributions to O–O Cleavage and the Resultant Intermediate Generated in Heme-Copper Oxidases

et al. 2019

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This study investigates the mechanism of O–O bond cleavage in heme-copper oxidase (HCO) enzymes, combining experimental and computational insights from enzyme intermediates and synthetic models. It is determined that HCOs undergo a proton-initiated O–O cleavage mechanism where a single water molecule in the active site enables proton transfer (PT) from the cross-linked tyrosine to a peroxo ligand bridging the heme FeIII and CuII, and multiple H-bonding interactions lower the tyrosine pKa. Due to sterics within the active site, the proton must either transfer initially to the O(Fe) (a high-energy intermediate), or from another residue over a ~10 Å distance to reach the O(Cu) atom directly. While the distance between the H+ donor (Tyr) and acceptor (O(Cu)) results in a barrier to PT, this separation is critical for the low barrier to O–O cleavage as it enhances backbonding from Fe into the O–O σ* orbital. Thus, PT from Tyr precedes O–O elongation and is rate-limiting, consistent with available kinetic data. The electron transfers from tyrosinate after the barrier via a superexchange pathway provided by the cross-link, generating intermediate PM. PM is evaluated using available experimental data. The geometric structure contains an FeIV=O that is H-bonded to the CuII-OH. The electronic structure is a singlet, where the FeIV and CuII are antiferromagnetically coupled through the H-bond between the oxo(Fe) and hydroxo(Cu) ligands, while the CuII and Tyr• are ferromagnetically coupled due their delocalization into orthogonal magnetic orbitals on the cross-linked His residue. These findings provide critical insights into the mechanism of efficient O2 reduction in HCOs, and the nature of the PM intermediate that couples this reaction to proton pumping.

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Section: Introductionmentioning

confidence: 99%