Comparative study of the nucleophilic attack step in the proteases catalytic activity: A theoretical study

Sebastián A. Cuesta, José R. Mora, Cesar H. Zambrano, F. Javier Torres, Luis Rincón

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

2 Citas (Scopus)


The nucleophilic attack step of the hydrolysis reaction mechanism of the glycine-glycine peptide bond mediated by the enzymatic action of various proteases was elucidated by means of DFT calculations. Five different protease models were considered; namely: cysteine (Cys), threonine (Thr), serine (Ser), aspartyl (Asp) proteases, and a metalloprotease containing zinc (Zn). The model was simplified in order to gain information about the nucleophilic attack in this type of reaction. As a comparative study, this work is focused on the trend in the reactivity of the models. According to the computed activation energies, the reactivity order was determined as follows Cys < Thr < Ser < Zn < Asp, being in all cases faster than the uncatalysed spontaneous hydrolysis. A further analysis of the reactions by means of the reaction force approach showed that the structural changes accounts for 65–90% of the total activation energy. Moreover, a natural bond orbital analysis allows the reactions to be classified as synchronous with a late transition state for all cases. Systems analogous to the Cys-protease can be proposed as a promising candidate for the design of mimetic systems capable to cleavage amide bonds.

Idioma originalInglés estadounidense
Número de artículoe1705412
PublicaciónMolecular Physics
EstadoPublicada - jul 17 2020
Publicado de forma externa

All Science Journal Classification (ASJC) codes

  • Biofísica
  • Biología molecular
  • Física de la materia condensada
  • Química física y teórica

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