A QM/MM Study on the Reaction Pathway Leading to 2-Aceto-2-Hydroxybutyrate in the Catalytic Cycle of AHAS

作者：Sanchez Leslie^*; Jana Gonzalo A; Delgado Eduardo J

来源：Journal of Computational Chemistry, 2014, 35(6): 488-494.

DOI：10.1002/jcc.23523

• acetodydroxy acid synthase
• catalytic cycle
• quantum
• molecular mechanical
• potential energy surface

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.

• 出版日期2014-3-5