Channelling of dioxygen into the respiratory enzyme

Abstract

Aerobic organisms utilize 0 2 to oxidize foodstuffs into CO 2 and water in order to liberate energy for the synthesis of ATP. The reduction of 0 2 is mainly catalyzed by a superfamily of enzymes, the haem-copper oxidases, which are structurally and functionally related, and may collectively be called 'respiratory enzyme' (das Atmungsferment); they typically contain a binuclear haem (Fea3)copper (Cu B ) centre to which the 0 2 is bound, and where it is reduced to water by electron and proton transfer. The reduction of 0 2 is linked to proton translocation across the mitochondrial or bacterial membrane, by which means energy is conserved for ATP synthesis [I]. Whilst much work has been done to understand the paths and mechanisms of electron and proton transfers in the respiratory enzyme, the approach of the substrate dioxygen to its site of binding has received less attention. The crystal structure of cytochrome aa 3 from P. denitrificans shows that the O2-binding haem is buried deeply in the membranous domain of subunit I [2]. Woodruff and co-workers [3] demonstrated that CO approaches the oxygen-binding site of the haem by way of Cu B. Verkhovsky et al. [4] found that this is likely to be the case also for 0 2 . Such results suggest that 0 2 might approach the haem iron via a specific path ( 'channel ') in the protein. The apparent second order rate constant of O 2 binding to the respiratory enzyme is ca. 10 8 M I s l , i.e. diffusion-controlled, and is at least 10-fold faster than 0 2 binding to most other haemoproteins [5]. This would also