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.
Further theoretical insight into the reaction mechanism of the hepatitis C NS3/NS4A serine protease / Martinez-Gonzalez, J. A.; Rodriguez Garcia, A.; Puyuelo, M. P.; Gonzalez, M.; Martinez, R.. - In: CHEMICAL PHYSICS LETTERS. - ISSN 0009-2614. - 619:(2015), pp. 97-102. [10.1016/j.cplett.2014.11.041]
Further theoretical insight into the reaction mechanism of the hepatitis C NS3/NS4A serine protease
Rodriguez Garcia, A.;
2015-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
