%0 Journal Article %1 RN394 %A Miranda-Rojas, S. %A Fernandez, I. %A Kastner, J. %A Toro-Labbe, A. %A Mendizabal, F. %D 2018 %J Chemcatchem %K activation analysis, approach, bond, carbon-fluorine catalysis, chemical cluster decomposition density-functional displacement, dqcauchile dynamics, energy enzyme force, mechanism model, molecular-orbital qm/mm, reaction s(n)2 strain theory, transition-state, %N 5 %P 1052-1063 %R 10.1002/cctc.201701517 %T Unraveling the Nature of the Catalytic Power of Fluoroacetate Dehalogenase %U /brokenurl#<Go to ISI>://WOS:000426844600026 %V 10 %X 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.

@article{RN394, 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.}, added-at = {2019-12-04T03:57:35.000+0100}, author = {Miranda-Rojas, S. and Fernandez, I. and Kastner, J. and Toro-Labbe, A. and Mendizabal, F.}, biburl = {https://www.bibsonomy.org/bibtex/2254968d84b6ef3ec3a8bca2eaadc2f50/dqcauchile}, doi = {10.1002/cctc.201701517}, interhash = {d464403ccc49ea069f5afda84b7c18cb}, intrahash = {254968d84b6ef3ec3a8bca2eaadc2f50}, issn = {1867-3880}, journal = {Chemcatchem}, keywords = {activation analysis, approach, bond, carbon-fluorine catalysis, chemical cluster decomposition density-functional displacement, dqcauchile dynamics, energy enzyme force, mechanism model, molecular-orbital qm/mm, reaction s(n)2 strain theory, transition-state,}, number = 5, pages = {1052-1063}, timestamp = {2019-12-04T03:58:17.000+0100}, title = {Unraveling the Nature of the Catalytic Power of Fluoroacetate Dehalogenase}, type = {Journal Article}, url = {/brokenurl#<Go to ISI>://WOS:000426844600026}, volume = 10, year = 2018 }