A structural and functional perspective on the evolution of the heme–copper oxidases

The heme-copper oxidases (HCOs) catalyze the reduction of O2 to water, and couple the free energy to proton pumping across the membrane. HCOs are divided into three sub-classes, A, B and C, whose order of emergence in evolution has been controversial. Here we have analyzed recent structural and functional data on HCOs and their homologues, the nitric oxide reductases (NORs). We suggest that the C-type oxidases are ancient enzymes that emerged from the NORs. In contrast, the A-type oxidases are the most advanced from both structural and functional viewpoints, which we interpret as evidence for having evolved later.