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

ABSTRACT: 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 Fe^III and Cu^II, and multiple H-bonding interactions lower the tyrosine p K_a. 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 accepto

SUBMITTER: Schaefer AW 

PROVIDER: S-EPMC6639083 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature