The Proton Pump of Cytochrome Oxidase

The Proton Pump of Cytochrome Oxidase

Abstract

Most respiratory oxygen reductases are members of a diverse superfamily of enzymes that also includes prokaryotic NO reductases. Most of our work has been on the most widely distributed family of respiratory oxidases, which are close homologues of the mammalian mitochondrial cytochrome c oxidase. These are classified as “A” type respiratory oxidases. These enzymes reduce oxygen to water, and use the available free energy to pump protons across the membrane and generate a proton motive force. Working with prokaryotic homologues of the mitochondrial enzymes, particularly from Rhodobacter sphaeroides, we have defined two proton-input channels, called the D- and K-channels. These two channels provide conduits for protons to reach the active site for the chemistry of reducing O2 to water, and also serve as a pathway for protons that are pumped across the membrane. Of particular interest is the behavior of mutations in a region near the entrance of the D channel which decouple enzyme turnover from the proton pump. These mutants support the proposal that all of the pumped protons, 4 per O2, pass through the D-channel.
While the mechanistic studies on the A type oxidases clearly implicates the D channel in proton pumping, it appears that during the course of evolution, alternative channels may have appeared.

Speaker: Robert B. Gennis

Affiliation: Department of Biochemistry, University of Illinois, USA

Host: Manuela M. Pereira