Plasticity of proton pathways in haem-copper oxygen reductases

Oxygen reductases are the final enzymes in the aerobic respiratory chains catalysing the reduction of dioxygen to water, with the concomitant translocation of protons through the bacterial cytoplasmatic or mitochondrial membranes. Most of these enzymes belong to the family of haem-copper oxygen reductases. Intraprotein proton-conducting pathways are needed for the chemical reaction and for the translocated protons. Based on sequence and structural analyses, and site-directed mutagenesis, two proton channels were established for the mitochondrial-like oxygen reductases. However, the amino acid residues forming these channels are not conserved among the family members. Most importantly, many oxygen reductases do not contain ionisable amino acid residues in the putative proton pathways nor in alternative positions. The diversity of channels in haem-copper oxygen reductases exemplifies the plasticity of proton pathways that occurred throughout evolution, and strongly suggests a substantial role for water as the main proton carrier.