A QM/MM study on the reaction pathway leading to 2-aceto-2-hydroxybutyrate in the catalytic cycle of AHAS.
J Comput Chem
; 35(6): 488-94, 2014 Mar 05.
Article
in En
| MEDLINE
| ID: mdl-24395707
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acetolactate Synthase
/
Butyrates
/
Amino Acids, Branched-Chain
/
Hydroxybutyrates
Language:
En
Journal:
J Comput Chem
Journal subject:
QUIMICA
Year:
2014
Document type:
Article