Increased Dynamic Effects in a Catalytically Compromised Variant of Escherichia coli Dihydrofolate Reductase
Ver/ Abrir
Impacto
Scholar |
Otros documentos de la autoría: Ruiz-Pernía, José Javier; Luk, Louis Y. P.; García Meseguer, Rafael; Martí Forés, Sergio; Loveridge, E. Joel; Tuñón, Iñaki; Moliner, Vicent; 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:
INVESTIGACIONMetadatos
Título
Increased Dynamic Effects in a Catalytically Compromised Variant of Escherichia coli Dihydrofolate ReductaseAutoría
Fecha de publicación
2013Editor
American Chemical SocietyISSN
0002-7863; 1520-5126Cita bibliográfica
RUIZ-PERNIA, J. Javier, et al. Increased dynamic effects in a catalytically compromised variant of Escherichia coli dihydrofolate reductase. Journal of the American Chemical Society, 2013, vol. 135, no 49, p. 18689-18696.Tipo de documento
info:eu-repo/semantics/articleVersión de la editorial
http://pubs.acs.org/doi/abs/10.1021/ja410519hVersión
info:eu-repo/semantics/publishedVersionPalabras clave / Materias
Resumen
Isotopic substitution (15N, 13C, 2H) of a catalytically compromised variant of Escherichia coli dihydrofolate reductase, EcDHFR-N23PP/S148A, has been used to investigate the effect of these mutations on catalysis. The ... [+]
Isotopic substitution (15N, 13C, 2H) of a catalytically compromised variant of Escherichia coli dihydrofolate reductase, EcDHFR-N23PP/S148A, has been used to investigate the effect of these mutations on catalysis. The reduction of the rate constant of the chemical step in the EcDHFR-N23PP/S148A catalyzed reaction is essentially a consequence of an increase of the quasi-classical free energy barrier and to a minor extent of an increased number of recrossing trajectories on the transition state dividing surface. Since the variant enzyme is less well set up to catalyze the reaction, a higher degree of active site reorganization is needed to reach the TS. Although millisecond active site motions are lost in the variant, there is greater flexibility on the femtosecond time scale. The “dynamic knockout” EcDHFR-N23PP/S148A is therefore a “dynamic knock-in” at the level of the chemical step, and the increased dynamic coupling to the chemical coordinate is in fact detrimental to catalysis. This finding is most likely applicable not just to hydrogen transfer in EcDHFR but also to other enzymatic systems. [-]
Publicado en
Journal of the American Chemical Society (2013) vol. 135, no 49Derechos de acceso
Copyright © American Chemical Society
http://rightsstatements.org/vocab/InC/1.0/
info:eu-repo/semantics/openAccess
http://rightsstatements.org/vocab/InC/1.0/
info:eu-repo/semantics/openAccess
Aparece en las colecciones
- QFA_Articles [830]