J. Hemp, C. Christian, B. Barquera, R. B. Gennis, and Todd J. Martinez
The heme-copper oxidase superfamily contains the terminal oxidases in the aerobic respiratory chains of prokaryotes and mitochondria which reduce oxygen and generate protonmotive force. Sequence analysis indicates that cbb3 oxidases are missing an active site Tyr residue which is absolutely conserved in all other oxidases. In other superfamily members, this Tyr is known to be subject to an unusual post-translational modification and to play a critical role in the catalytic mechanism. The absence of this Tyr raises the possibility of differing mechanisms in cbb3 and other oxidases. Using homology modeling, quantum chemistry, and molecular dynamics, the structure of subunit I for a cbb3 oxidase (Vibrio cholerae) is predicted. A Tyr residue structurally analogous to the active-site Tyr in other oxidases is found, but originating from a different transmembrane helix. This active-site Tyr could, in principle, also be subject to the post-translational modification observed in other oxidase structures. These findings strongly suggest that all of the oxidases utilize the same catalytic mechanism and provide a unique example of compensatory mutation involving an active-site residue which is post-translationally modified.