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Electrostatic interactions contribute to the control of intramolecular thiol-disulfide isomerization in a protein

Maag, D. ORCID iD icon; Putzu, M.; Gómez-Flores, C. L.; Gräter, F.; Elstner, M.; Kubař, T.


The roles of structural factors and of electrostatic interactions with the environment on the outcome of thiol–disulfide exchange reactions were investigated in a mutated immunoglobulin domain (I27*) under mechanical stress. An extensive ensemble of molecular dynamics trajectories was generated by means of QM/MM simulations for a total sampling of 5.7 μs. A significant number of thiol–disulfide exchanges were observed, and the Cys32 thiolate preferred to attack Cys55 over Cys24, in agreement with previous experimental and computational studies. The structural features as well as electronic structures of the thiol–disulfide system along the reaction were analyzed, as were the electrostatic interactions with the environment. The previous findings of better accessibility of Cys55 were confirmed. Additionally, the reaction was found to be directed by the electrostatic interactions of the involved sulfur atoms with the molecular environment. The relationships of atomic charges, which stem from the electrostatic interactions, lead to the kinetic preference of the attack on Cys55. Further, QM/MM metadynamics simulations of thiol–disulfide exchange in a small model system with varied artificial external electric potentials revealed changes in reaction kinetics of the same magnitude as in I27*. ... mehr

Verlagsausgabe §
DOI: 10.5445/IR/1000141112
Veröffentlicht am 15.12.2021
DOI: 10.1039/d1cp03129e
Zitationen: 5
Web of Science
Zitationen: 4
Zitationen: 6
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische Grenzflächen (IBG)
Institut für Physikalische Chemie (IPC)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2021
Sprache Englisch
Identifikator ISSN: 1463-9076, 1463-9084
KITopen-ID: 1000141112
HGF-Programm 47.14.01 (POF IV, LK 01) Molekular Information Processing in Cellular Systems
Erschienen in Physical Chemistry Chemical Physics
Verlag Royal Society of Chemistry (RSC)
Band 23
Heft 46
Seiten 26366-26375
Vorab online veröffentlicht am 11.11.2021
Nachgewiesen in Dimensions
Web of Science
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