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A QM/MM study on the reaction pathway leading to 2‐Aceto‐2‐hydroxybutyrate in the catalytic cycle of AHAS
Author(s) -
Sánchez Leslie,
Jaña Gonzalo A.,
Delgado Eduardo J.
Publication year - 2014
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.23523
Subject(s) - qm/mm , catalysis , chemistry , activation barrier , catalytic cycle , molecule , proton , reaction mechanism , atp synthase , stereochemistry , transition state , computational chemistry , enzyme , biochemistry , organic chemistry , physics , quantum mechanics
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.