Further theoretical insight into the reaction mechanism of the hepatitis C NS3/NS4A serine protease

José Ángel Martínez-González, Alex Rodríguez, María Pilar Puyuelo, Miguel González, Rodrigo Martínez

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    Abstract

    © 2014 Elsevier B.V. All rights reserved. The main reactions of the hepatitis C virus NS3/NS4A serine protease are studied using the second-order Møller-Plesset ab initio method and rather large basis sets to correct the previously reported AM1/CHARMM22 potential energy surfaces. The reaction efficiencies measured for the different substrates are explained in terms of the tetrahedral intermediate formation step (the rate-limiting process). The energies of the barrier and the corresponding intermediate are so close that the possibility of a concerted mechanism is open (especially for the NS5A/5B substrate). This is in contrast to the suggested general reaction mechanism of serine proteases, where a two-step mechanism is postulated.
    Original languageEnglish
    Pages (from-to)97-102
    JournalChemical Physics Letters
    Volume619
    DOIs
    Publication statusPublished - 5 Jan 2015

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    Martínez-González, J. Á., Rodríguez, A., Puyuelo, M. P., González, M., & Martínez, R. (2015). Further theoretical insight into the reaction mechanism of the hepatitis C NS3/NS4A serine protease. Chemical Physics Letters, 619, 97-102. https://doi.org/10.1016/j.cplett.2014.11.041