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

  1. Martínez-González, J.Á. 24
  2. Rodríguez, A. 3
  3. Puyuelo, M.P. 2
  4. González, M. 1
  5. Martínez, R. 2
  1. 1 Universitat de Barcelona
    info

    Universitat de Barcelona

    Barcelona, España

    ROR https://ror.org/021018s57

  2. 2 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

  3. 3 International School for Advanced Studies
    info

    International School for Advanced Studies

    Trieste, Italia

    ROR https://ror.org/004fze387

  4. 4 Universitat Autònoma de Barcelona
    info

    Universitat Autònoma de Barcelona

    Barcelona, España

    ROR https://ror.org/052g8jq94

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Revista:
Chemical Physics Letters

ISSN: 0009-2614

Año de publicación: 2015

Volumen: 619

Páginas: 97-102

Tipo: Artículo

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DOI: 10.1016/J.CPLETT.2014.11.041 SCOPUS: 2-s2.0-84916926155 WoS: WOS:000347104600020 GOOGLE SCHOLAR

Otras publicaciones en: Chemical Physics Letters

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Resumen

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.