Evolution of structure and function of human peroxidases

Abstract

Four heme superfamilies arose independently during evolution, which differ in overall fold, active site architecture and enzymatic activities. The redox cofactor is heme b or posttranslationally modified heme that is ligated by either histidine or cysteine. Here we describe the evolution of the peroxidase-cyclooxygenase superfamily which is the only superfamily having the prosthetic group covalently linked via one-, two or three bonds with the protein. It is comprised of seven families with the chordata peroxidases forming the latest evolutionary descendants including thyroid peroxidase, lactoperoxidase (LPO), eosinophil peroxidase and myeloperoxidase (MPO). Based on an updated phylogenetic tree, the available X-ray structures (MPO, LPO), biophysical and kinetic investigations, we analyse the evolution of structure and function of chordata heme peroxidases as well as their relation to other (multidomain) families of this superfamily. Among other aspects the roles of the heme to protein linkages in redox chemistry and catalysis are presented. Finally, it is discussed how these biochemical properties are related to the physiological roles of these peroxidases.