TY - JOUR
T1 - Further theoretical insight into the reaction mechanism of the hepatitis C NS3/NS4A serine protease
AU - Martínez-González, José Ángel
AU - Rodríguez, Alex
AU - Puyuelo, María Pilar
AU - González, Miguel
AU - Martínez, Rodrigo
PY - 2015/1/5
Y1 - 2015/1/5
N2 - © 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.
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.
U2 - 10.1016/j.cplett.2014.11.041
DO - 10.1016/j.cplett.2014.11.041
M3 - Article
VL - 619
SP - 97
EP - 102
JO - Chemical Physics Letters
JF - Chemical Physics Letters
SN - 0009-2614
ER -
