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Energetics of the proposed rate‐determining step of the glyoxalase I reaction
Author(s) -
Feierberg Isabella,
Cameron Alexander D.,
Åqvist Johan
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00703-6
Subject(s) - chemistry , catalysis , reaction rate constant , rate determining step , reaction rate , proton , energetics , computational chemistry , molecular dynamics , kinetics , activation energy , valence bond theory , ion , thermodynamics , molecule , organic chemistry , molecular orbital , physics , quantum mechanics
The proposed rate‐limiting step of the reaction catalyzed by glyoxalase I is the proton abstraction from the C1 carbon atom of the substrate by a glutamate residue, resulting in a high‐energy enolate intermediate. This proton transfer reaction was modelled using molecular dynamics and free energy perturbation simulations, with the empirical valence bond method describing the potential energy surface of the system. The calculated rate constant for the reaction is approximately 300–1500 s −1 with Zn 2+ , Mg 2+ or Ca 2+ bound to the active site, which agrees well with observed kinetics of the enzyme. Furthermore, the results imply that the origin of the catalytic rate enhancement is mainly associated with enolate stabilization by the metal ion.