Unraveling the role of protein dynamics in dihydrofolate reductase catalysis
Impacto
Scholar |
Otros documentos de la autoría: Moliner, Vicent; Ruiz-Pernía, José Javier; Luk, Louis Y. P.; Dawson, William M.; Roca, Maite; Loveridge, E. Joel; Glowacki, David R.; Harvey, Jeremy N.; Mulholland, Adrian J.; Tuñón, Iñaki; Allemann, Rudolf K.
Metadatos
Mostrar el registro completo del ítemcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/7013
comunitat-uji-handle3:10234/8638
comunitat-uji-handle4:
INVESTIGACIONEste recurso está restringido
http://dx.doi.org/10.1073/pnas.1312437110 |
Metadatos
Título
Unraveling the role of protein dynamics in dihydrofolate reductase catalysisAutoría
Fecha de publicación
2013Editor
National Academy of SciencesISSN
0027-8424Cita bibliográfica
LUK, Louis YP, et al. Unraveling the role of protein dynamics in dihydrofolate reductase catalysis. Proceedings of the National Academy of Sciences, 2013, vol. 110, no 41, p. 16344-16349Tipo de documento
info:eu-repo/semantics/articleVersión de la editorial
http://www.pnas.org/content/110/41/16344.full.pdf+htmlVersión
info:eu-repo/semantics/publishedVersionPalabras clave / Materias
Resumen
Protein dynamics have controversially been proposed to be at the heart of enzyme catalysis, but identification and analysis of dynamical effects in enzyme-catalyzed reactions have proved very challenging. Here, we ... [+]
Protein dynamics have controversially been proposed to be at the heart of enzyme catalysis, but identification and analysis of dynamical effects in enzyme-catalyzed reactions have proved very challenging. Here, we tackle this question by comparing an enzyme with its heavy (15N, 13C, 2H substituted) counterpart, providing a subtle probe of dynamics. The crucial hydride transfer step of the reaction (the chemical step) occurs more slowly in the heavy enzyme. A combination of experimental results, quantum mechanics/molecular mechanics simulations, and theoretical analyses identify the origins of the observed differences in reactivity. The generally slightly slower reaction in the heavy enzyme reflects differences in environmental coupling to the hydride transfer step. Importantly, the barrier and contribution of quantum tunneling are not affected, indicating no significant role for “promoting motions” in driving tunneling or modulating the barrier. The chemical step is slower in the heavy enzyme because protein motions coupled to the reaction coordinate are slower. The fact that the heavy enzyme is only slightly less active than its light counterpart shows that protein dynamics have a small, but measurable, effect on the chemical reaction rate. [-]
Publicado en
Proceedings of the National Academy of Sciences ( 2013) vol. 110, no 41Derechos de acceso
© National Academy of Sciences
http://rightsstatements.org/vocab/InC/1.0/
info:eu-repo/semantics/restrictedAccess
http://rightsstatements.org/vocab/InC/1.0/
info:eu-repo/semantics/restrictedAccess
Aparece en las colecciones
- QFA_Articles [829]