Computer-assisted study on the reaction between pyruvate and ylide in the pathway leading to lactyl-ThDP.
In this study the formation of the lactyl-thiamin diphosphate intermediate (L-ThDP) is addressed using density functional theory calculations at X3LYP/6-31++G(d,p) level of theory. The study includes potential energy surface scans, transition state search, and intrinsic reaction coordinate calculations. Reactivity is analyzed in terms of Fukui functions. The results allow to conclude that the reaction leading to the formation of L-ThDP occurs via a concerted mechanism, and during the nucleophilic attack on the pyruvate molecule, the ylide is in its AP form. The calculated activation barrier for the reaction is 19.2 kcal/mol, in agreement with the experimental reported value.
Computational Biological Chemistry Group (QBC), Universidad de Concepción, Concepción, Chile.
Omar
O
Alvarado
Gonzalo
G
Jaña
Eduardo J
EJ
Delgado
D001665:Binding Sites; D002384:Catalysis; D003198:Computer Simulation; D008956:Models, Chemical; D019289:Pyruvic Acid / Q000737:chemistry*; D013816:Thermodynamics; D013835:Thiamine Pyrophosphate / Q000031:analogs & derivatives* / Q000737:chemistry
C497352:C2-alpha-lactylthiamin diphosphate; D019289:Pyruvic Acid; D013835:Thiamine Pyrophosphate