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

Abstract
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.