A QM/MM study on the reaction pathway leading to 2‐Aceto‐2‐hydroxybutyrate in the catalytic cycle of AHAS |
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Authors: | Leslie Sánchez Gonzalo A. Jaña Eduardo J. Delgado |
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Affiliation: | 1. Computational Biological Chemistry Group, Faculty of Chemical Sciences, Universidad de Concepción, Concepción;2. Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Sede Concepción, Universidad Andrés Bello, Concepcion |
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Abstract: | The reaction between the intermediate 2‐hydroxyethyl‐thiamin diphosphate (HEThDP?) and 2‐ketobutyrate, in the third step of the catalytic cycle of acetodydroxy acid synthase, is addressed from a theoretical point of view by means of hybrid quantum/molecular mechanical calculations. The QM region includes one molecule of 2‐ketobutyrate, the HEThDP? intermediate, and the residues Arg 380 y Glu 139; whereas the MM region includes the rest of the protein. The study includes potential energy surface scans to identify and characterize critical points on it, transition state search and activation barrier calculations. The results show that the reaction occurs via a two‐step mechanism corresponding to the carboligation and proton transfer in the first stage; and the product release in the second step. © 2014 Wiley Periodicals, Inc. |
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Keywords: | acetodydroxy acid synthase catalytic cycle quantum/molecular mechanical potential energy surface |
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