Biochemistry of Copper Site Assembly in Heme-Copper Oxidases: A Theme with Variations.

Copper is an essential cofactor for aerobic respiration, since it is required as a redox cofactor in Cytochrome Oxidase (COX). This ancient and highly conserved enzymatic complex from the family of heme-copper oxidase possesses two copper sites: Cu and Cu. Biosynthesis of the oxidase is a complex, stepwise process that requires a high number of assembly factors. In this review, we summarize the state-of-the-art in the assembly of COX, with special emphasis in the assembly of copper sites. Assembly of the Cu site is better understood, being at the same time highly variable among organisms. We also discuss the current challenges that prevent the full comprehension of the mechanisms of assembly and the pending issues in the field.