Publicación:
Mechanistic insights into the phosphoryl transfer reaction in cyclin-dependent kinase 2: A QM/MM study

Vista sencilla de ítem
dc.contributor.authorRecabarren, Rodrigo
dc.contributor.authorOsorio, Edison H.
dc.contributor.authorCaballlero, Julio
dc.contributor.authorTuñón, Iñaki
dc.contributor.authorAlzate-Morales, Jans H.
dc.date.accessioned2019-12-13T17:48:10Z
dc.date.available2019-12-13T17:48:10Z
dc.date.issued2019-09-04
dc.description.abstractCyclin-dependent kinase 2 (CDK2) is an important member of the CDK family exerting its most important function in the regulation of the cell cycle. It catalyzes the transfer of the gamma phosphate group from an ATP (adenosine triphosphate) molecule to a Serine/Threonine residue of a peptide substrate. Due to the importance of this enzyme, and protein kinases in general, a detailed understanding of the reaction mechanism is desired. Thus, in this work the phosphoryl transfer reaction catalyzed by CDK2 was revisited and studied by means of hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. Our results suggest that the base-assisted mechanism is preferred over the substrate-assisted pathway when one Mg2+ is present in the active site, in agreement with a previous theoretical study. The base-assisted mechanism resulted to be dissociative, with a potential energy barrier of 14.3 kcal/mol, very close to the experimental derived value. An interesting feature of the mechanism is the proton transfer from Lys129 to the phosphoryl group at the second transition state, event that could be helping in neutralizing the charge on the phosphoryl group upon the absence of a second Mg2+ ion. Furthermore, important insights into the mechanisms in terms of bond order and charge analysis were provided. These descriptors helped to characterize the synchronicity of bond forming and breaking events, and to characterize charge transfer effects. Local interactions at the active site are key to modulate the charge distribution on the phosphoryl group and therefore alter its reactivity.es_CO
dc.description.sponsorshipUniversidad de Ibaguées_CO
dc.identifier.citationRecabarren R, Osorio EH, Caballero J, Tuñón I, Alzate-Morales JH (2019) Mechanistic insights into the phosphoryl transfer reaction in cyclin-dependent kinase 2: A QM/MM study. PLoS ONE 14(9): e0215793. https://doi.org/10.1371/journal.pone.0215793es_CO
dc.identifier.issn1932-6203
dc.identifier.urihttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215793
dc.language.isoenes_CO
dc.publisherPlos Onees_CO
dc.subjectCyclin-dependent kinase 2 (CDK2)es_CO
dc.subjectReaction mechanismes_CO
dc.subjectQuantum mechanics/molecular mechanics (QM/MM) calculations.es_CO
dc.titleMechanistic insights into the phosphoryl transfer reaction in cyclin-dependent kinase 2: A QM/MM studyes_CO
dc.typeArticlees_CO
dspace.entity.typePublication
eperson.emailedison.osorio@unibague.edu.coes_CO
Archivos
Bloque de licencias
Mostrando1 - 1 de 1
Miniatura
Nombre:
license.txt
Tamaño:
134 B
Formato:
Item-specific license agreed upon to submission
Descripción:
Descargar
Colecciones
Artículos