Cytochrome cbb3 is a distinct member of the superfamily of respiratory heme-copper oxidases, and is responsible for driving the respiratory chain in many pathogenic bacteria. Like the canonical heme-copper oxidases, cytochrome cbb3 reduces oxygen to water and couples the released energy to pump protons across the bacterial membrane. Homology modeling and recent electron paramagnetic resonance (EPR) studies on wild type and a mutant cbb3 enzyme [V. Rauhamäki et al. J. Biol. Chem. 284 (2009) 11301-11308] have led us to perform high-level quantum chemical calculations on the active site. These calculations bring molecular insight into the unique hydrogen bonding between the proximal histidine ligand of heme b3 and a conserved glutamate, and indicate that the catalytic mechanism involves redox-coupled proton transfer between these residues. The calculated spin densities give insight in the difference in EPR spectra for the wild type and a recently studied E383Q-mutant cbb3-enzyme. Furthermore, we show that the redox-coupled proton movement in the proximal cavity of cbb3-enzymes contributes to the low redox potential of heme b3, and suggest its potential implications for the high apparent oxygen affinity of these enzymes. © 2010 Elsevier B.V.
Sharma, V., Wikström, M., & Kaila, V. R. I. (2010). Redox-coupled proton transfer in the active site of cytochrome cbb3. Biochimica et Biophysica Acta - Bioenergetics, 1797(8), 1512–1520. https://doi.org/10.1016/j.bbabio.2010.03.004