Dl. Rousseau et al., PROTON TRANSLOCATION IN CYTOCHROME-C-OXIDASE - REDOX LINKAGE THROUGH PROXIMAL LIGAND-EXCHANGE ON CYTOCHROME-A3, Journal of bioenergetics and biomembranes, 25(2), 1993, pp. 165-176
An analysis of resonance Raman scattering data from CO-bound cytochrom
e c oxidase and from the photodissociated enzyme indicates that histid
ine may not be coordinated to the iron atom of cytochrome a3 in the CO
-bound form of the enzyme. Instead, the data suggest that either a wat
er molecule or a different amino acid residue occupies the proximal li
gand position. From these data, it is postulated that ligand exchange
on cytochrome a3 can occur under physiological conditions. Studies of
mutant hemoglobins have demonstrated that tyrosinate binds preferentia
lly to histidine in the ferric forms of the proteins. In cytochrome c
oxidase tyrosine residues are located near the histidine residues rece
ntly implicated in coordination to cytochrome a3 (Shapleigh et al., 19
92; Hosler et al., this volume). Expanding on these concepts, we propo
se a model for proton translocation at the 02-binding site based on pr
oximal ligand exchange between tyrosine and histidine on cytochrome a3
. The pumping steps take place at the level of the peroxy intermediate
and at the level of the ferryl intermediate in the catalytic cycle an
d are thereby consistent with the recent results of Wilkstrom (1989) w
ho found that proton pumping occurs only at these two steps. It is sho
wn that the model may be readily extended to account for the pumping o
f two protons at each of the steps.