New Insights on the Reaction Pathway Leading to Lactyl-ThDP: A Theoretical Approach

Ignacio Lizana, Gonzalo A. Jaña, Eduardo J. Delgado

Resultado de la investigación: Contribución a una revistaArtículo

3 Citas (Scopus)


In all ThDP-dependent enzymes, the catalytic cycle is initiated with the attack of the C2 atom of the ylide intermediate on the Cα atom of a pyruvate molecule to form the lactyl-ThDP (L-ThDP) intermediate. In this study, the reaction between the ylide intermediate and pyruvate leading to the formation of L-ThDP is addressed from a theoretical point of view. The study includes molecular dynamics, exploration of the potential energy surface by means of QM/MM calculations, and reactivity analysis on key centers. The results show that the reaction occurs via a concerted mechanism in which the carboligation and the proton transfers occur synchronically. It is also observed that during the reaction the protonation state of the N1′ atom changes: the reaction starts with the ylide having the N1′ atom deprotonated and reaches a transition state showing the N1′ atom protonated. This conversion leads to the reaction path of minimum energy, with an activation energy of about 20 kcal mol-1. On the other hand, it is also observed that the approaching distance between the pyruvate and the ylide, i.e., the Cα-C2 distance, plays a fundamental role in the reaction mechanism since it determines the nucleophilic character of key atoms of the ylide, which in turn trigger the elemental reactions of the mechanism. (Figure Presented).

Idioma originalInglés
Páginas (desde-hasta)1640-1644
Número de páginas5
PublicaciónJournal of Chemical Information and Modeling
EstadoPublicada - 24 ago 2015

Áreas temáticas de ASJC Scopus

  • Química (todo)
  • Ingeniería química (todo)
  • Informática aplicada
  • Biblioteconomía y ciencias de la información
  • Medicina (todo)

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