Revealing the Deactivation Mechanism of Aconitase at the Atomistic Level by Multiscale Simulations
- 1Institute for Theoretical Chemistry, University of Stuttgart, Pfaffenwaldring 55, Stuttgart, Germany, 70569
- 2SC SimTech, University of Stuttgart, Universitätstraße 32, Stuttgart, Germany, 70569
Abstract
Mitochondrial aconitase is a key enzyme of the citric acid cycle that converts citrate to isocitrate at its [4 Fe−4 S] cluster cofactor. It is widely conserved across vertebrates and also found in numerous other organisms. Oxidation of the [4 Fe−4 S] cluster by reactive oxygen and nitrogen species (ROS/RNS) leads to the release of one Fe center, denoted as Fe α . The remaining [3 Fe−4 S] cluster is catalytically inactive, meaning aconitase oxidation leads to enzyme deactivation. Aconitase deactivation regulates the citric acid cycle and mitochondrial respiration, which leads to decreased ROS and RNS formation. Thus, aconitase serves as a redox sensor that prevents high ROS and RNS concentrations. The deactivation process is well characterized on the macroscopic scale, meaning that the deactivation kinetics and the thermodynamics of oxidation are known.
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BibTeX
@misc{stier2026revealing,
title = {{Revealing the Deactivation Mechanism of Aconitase at the Atomistic Level by Multiscale Simulations}},
author = {Michael Stier and Kristyna Pluhackova and Johannes Kästner},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15009474/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009474/v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Revealing the Deactivation Mechanism of Aconitase at the Atomistic Level by Multiscale Simulations
AU - Michael Stier
AU - Kristyna Pluhackova
AU - Johannes Kästner
PY - 2026
DA - 2026/09/25
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009474/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009474/v1
AB - Mitochondrial aconitase is a key enzyme of the citric acid cycle that converts citrate to isocitrate at its [4 Fe−4 S] cluster cofactor. It is widely conserved across vertebrates and also found in numerous other organisms. Oxidation of the [4 Fe−4 S] cluster by reactive oxygen and nitrogen species (ROS/RNS) leads to the release of one Fe center, denoted as Fe α . The remaining [3 Fe−4 S] cluster is catalytically inactive, meaning aconitase oxidation leads to enzyme deactivation. Aconitase deactivation regulates the citric acid cycle and mitochondrial respiration, which leads to decreased ROS and RNS formation. Thus, aconitase serves as a redox sensor that prevents high ROS and RNS concentrations. The deactivation process is well characterized on the macroscopic scale, meaning that the deactivation kinetics and the thermodynamics of oxidation are known.
ER -