Force-activated reactivity switch in a bimolecular chemical reaction
Author: ["Sergi Garcia-Manyes","Jian Liang","Robert Szoszkiewicz","Tzu-Ling Kuo","Julio M. Fernández"]
Publication: Nature Chemistry
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Abstract
The effect of mechanical force on the free-energy surface that governs a chemical reaction is largely unknown. The combination of protein engineering with single-molecule force-clamp spectroscopy allows us to study the influence of mechanical force on the rate at which a protein disulfide bond is reduced by nucleophiles in a bimolecular substitution reaction (SN2). We found that cleavage of a protein disulfide bond by hydroxide anions exhibits an abrupt reactivity ‘switch’ at ∼500 pN, after which the accelerating effect of force on the rate of an SN2 chemical reaction greatly diminishes. We propose that an abrupt force-induced conformational change of the protein disulfide bond shifts its ground state, drastically changing its reactivity in SN2 chemical reactions. Our experiments directly demonstrate the action of a force-activated switch in the chemical reactivity of a single molecule. Mechanical stretching of a protein can be studied in detail using single-molecule experiments, and is shown to have an accelerating effect on its reaction with a nucleophile. The observation of a dramatic switch in the effect above a threshold force suggests an abrupt change in protein conformation and a change in reaction mechanism.
Cite this article
Garcia-Manyes, S., Liang, J., Szoszkiewicz, R. et al. Force-activated reactivity switch in a bimolecular chemical reaction. Nature Chem 1, 236–242 (2009). https://doi.org/10.1038/nchem.207
