Hydrogen bonding rearrangement by a mitochondrial disease mutation in cytochrome bc1 perturbs heme bH redox potential and spin state

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Kuleta , P , Lasham , J , Sarewicz , M , Ekiert , I , Sharma , V , Ekiert , R & Osyczka , A 2021 , ' Hydrogen bonding rearrangement by a mitochondrial disease mutation in cytochrome bc1 perturbs heme bH redox potential and spin state ' , Proceedings of the National Academy of Sciences of the United States of America , vol. 118 , no. 33 , 2026169118 . https://doi.org/10.1073/pnas.2026169118

Title: Hydrogen bonding rearrangement by a mitochondrial disease mutation in cytochrome bc1 perturbs heme bH redox potential and spin state
Author: Kuleta, Patryk; Lasham, Jonathan; Sarewicz, Marcin; Ekiert, Iwona; Sharma, Vivek; Ekiert, Robert; Osyczka, Artur
Contributor: University of Helsinki, Doctoral Programme in Materials Research and Nanosciences
University of Helsinki, Institute of Biotechnology
Date: 2021-08-17
Language: eng
Number of pages: 10
Belongs to series: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
URI: http://hdl.handle.net/10138/333915
Abstract: Hemes are common elements of biological redox cofactor chains involved in rapid electron transfer. While the redox properties of hemes and the stability of the spin state are recognized as key determinants of their function, understanding the molecular basis of control of these properties is challenging. Here, benefiting from the effects of one mitochondrial disease-related point mutation in cytochrome b, we identify a dual role of hydrogen bonding (H-bond) to the propionate group of heme bH of cytochrome bc1, a common component of energy-conserving systems. We found that replacing conserved glycine with serine in the vicinity of heme bH caused stabilization of this bond, which not only increased the redox potential of the heme but also induced structural and energetic changes in interactions between Fe ion and axial histidine ligands. The latter led to a reversible spin conversion of the oxidized Fe from 1/2 to 5/2, an effect that potentially reduces the electron transfer rate between the heme and its redox partners. We thus propose that H-bond to the propionate group and heme-protein packing contribute to the fine-tuning of the redox potential of heme and maintaining its proper spin state. A subtle balance is needed between these two contributions: While increasing the H-bond stability raises the heme potential, the extent of increase must be limited to maintain the low spin and diamagnetic form of heme. This principle might apply to other native heme proteins and can be exploited in engineering of artificial hemecontaining protein maquettes.
Subject: 114 Physical sciences
mitochondrial dysfunction
electron paramagnetic resonance
molecular dynamics simulations
density functional theory
electron transfer
RHODOBACTER-CAPSULATUS
UBIQUINOL-CYTOCHROME-C2 OXIDOREDUCTASE
CORRELATION-ENERGY
ELECTRON-TRANSFER
BIS-HISTIDINE
COMPLEX-III
Q(O) SITE
DYNAMICS
BC(1)
INTERFACE
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