2018 |
Miranda-Rojas, S; Fernandez, I; Kastner, J; Toro-Labbe, A; Mendizabal, F Unraveling the Nature of the Catalytic Power of Fluoroacetate Dehalogenase Artículo de revista Chemcatchem, 10 (5), pp. 1052-1063, 2018, ISSN: 1867-3880. Resumen | Enlaces | BibTeX | Etiquetas: approach, bond, carbon-fluorine catalysis, chemical cluster decomposition density-functional displacement, dynamics, energy enzyme force, mechanism model, molecular-orbital qm/mm, transition-state @article{RN394, title = {Unraveling the Nature of the Catalytic Power of Fluoroacetate Dehalogenase}, author = { S. Miranda-Rojas and I. Fernandez and J. Kastner and A. Toro-Labbe and F. Mendizabal}, url = {/brokenurl#<Go to ISI>://WOS:000426844600026}, doi = {10.1002/cctc.201701517}, issn = {1867-3880}, year = {2018}, date = {2018-01-01}, journal = {Chemcatchem}, volume = {10}, number = {5}, pages = {1052-1063}, abstract = {Fluoroacetate dehalogenase is able to cleavage a carbon-fluoride bond, the strongest carbon-halogen bond in nature, in a process initiated by a S(N)2 reaction. The role of the enzyme machinery and particularly of the halogen pocket in the S(N)2 reaction is thoroughly explored by using state-of-the-art computational tools. A comparison between the non-catalyzed versus enzyme-catalyzed reaction, as well as with a mutant of the enzyme (Tyr219Phe), is presented. The energy barrier changes are rationalized by means of reaction force analysis and the activation strain model coupled with energy decomposition analysis. The catalysis is in part caused by the reduction of structural work from bringing the reactant species towards the proper reaction orientation, and the reduction of the electrostatic repulsion between the nucleophile and the substrate, which are both negatively charged. In addition, catalysis is also driven by an important reduction of the electronic reorganization processes during the reaction, where Tyr from the halogen pocket acts as a charge acceptor from the S(N)2 reaction axis therefore reducing the electronic steric repulsion between the reacting parts.}, keywords = {approach, bond, carbon-fluorine catalysis, chemical cluster decomposition density-functional displacement, dynamics, energy enzyme force, mechanism model, molecular-orbital qm/mm, transition-state}, pubstate = {published}, tppubtype = {article} } Fluoroacetate dehalogenase is able to cleavage a carbon-fluoride bond, the strongest carbon-halogen bond in nature, in a process initiated by a S(N)2 reaction. The role of the enzyme machinery and particularly of the halogen pocket in the S(N)2 reaction is thoroughly explored by using state-of-the-art computational tools. A comparison between the non-catalyzed versus enzyme-catalyzed reaction, as well as with a mutant of the enzyme (Tyr219Phe), is presented. The energy barrier changes are rationalized by means of reaction force analysis and the activation strain model coupled with energy decomposition analysis. The catalysis is in part caused by the reduction of structural work from bringing the reactant species towards the proper reaction orientation, and the reduction of the electrostatic repulsion between the nucleophile and the substrate, which are both negatively charged. In addition, catalysis is also driven by an important reduction of the electronic reorganization processes during the reaction, where Tyr from the halogen pocket acts as a charge acceptor from the S(N)2 reaction axis therefore reducing the electronic steric repulsion between the reacting parts. |
2018 |
Unraveling the Nature of the Catalytic Power of Fluoroacetate Dehalogenase Artículo de revista Chemcatchem, 10 (5), pp. 1052-1063, 2018, ISSN: 1867-3880. |