Significant Increase of Oxidase Activity through the Genetic Incorporation of a Tyrosine–Histidine Cross-Link in a Myoglobin Model of Heme–Copper Oxidase†

Xiaohong Liu1,‡, Yang Yu2,‡, Cheng Hu1, Wei Zhang1, Prof. Dr. Yi Lu2,*, Prof. Dr. Jiangyun Wang1,*

Keywords:enzyme catalysis;enzyme models;oxygen reduction;post‒translational modifications;protein design Top model: Heme–copper oxidase (HCO) contains a histidine–tyrosine cross-link in its heme a3/CuB oxygen reduction center. A functional model of HCO was obtained through the genetic incorporation of the unnatural amino acid imiTyr, which mimics the Tyr–His cross-link, and of the CuB site into myoglobin (see picture). Like HCO, this small soluble protein exhibits selective O2-reduction activity while generating little reactive oxygen species.