Hydrogen bonding rearrangement by a mitochondrial disease mutation in cytochrome bc ₁ perturbs heme b _H redox potential and spin state

Significance To perform their specific electron-transfer relay functions, hemes commonly adopt low spin states with fine-tuned redox potentials. Understanding molecular elements controlling these properties is crucial for the description of natural proteins and engineering redox-active systems. We describe unusual effects of mitochondrial disease-related mutation in cytochrome bc 1 , based on which we identify a dual role of hydrogen bonding to the propionate group of heme b H . We observe that stabilization of the hydrogen bond in mutant enhances the redox potential but destabilizes the low spin state of oxidized heme. This demonstrates a critical role of the hydrogen bonding, and heme-protein interactions in general, to secure a suitable redox potential and spin state, a notion that might be universal for other heme proteins.