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

doi:10.1016/j.cplett.2014.11.041

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

Research output: Contribution to journal › Article › Research › peer-review

1 Citation (Scopus)

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 language	English
Pages (from-to)	97-102
Journal	Chemical Physics Letters
Volume	619
DOIs	https://doi.org/10.1016/j.cplett.2014.11.041
Publication status	Published - 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

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AU - Martínez-González, José Ángel

AU - Rodríguez, Alex

AU - Puyuelo, María Pilar

AU - González, Miguel

AU - Martínez, Rodrigo

PY - 2015/1/5

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AB - © 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.

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JF - Chemical Physics Letters

SN - 0009-2614

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