THE HISTIDINE CYCLE - A NEW MODEL FOR PROTON TRANSLOCATION IN THE RESPIRATORY HEME-COPPER OXIDASES

A model of redox-linked proton translocation is presented for the term inal heme-copper oxidases. The new model, which is distinct both in pr inciple and in detail from previously suggested mechanisms, is introdu ced in a historical perspective and outlined first as a set of general principles, and then as a more detailed chemical mechanism, adapted t o what is known about the chemistry of dioxygen reduction in this fami ly of enzymes. The model postulates a direct mechanistic role in proto n-pumping of the oxygenous ligand on the iron in the binuclear heme-co pper site through an electrostatic nonbonding interaction between this ligand and the doubly protonated imidazolium group of a conserved his tidine residue nearby. In the model this histidine residue cycles betw een imidazolium and imidazolate states translocating two protons per e vent, the imidazolate state stabilized by bonding to the copper in the site. The model also suggests a key role in proton translocation for those protons that are taken up in reduction of O-2 to water, in that their uptake to the oxygenous ligand unlatches the electrostatically s tabilized imidazolium residue and promotes proton release.