TY - JOUR
T1 - A molecular dynamics study on the role of the protonation state in the biosynthesis of R-PAC by AHAS
AU - Alvarado, Omar
AU - García-Meseguer, Rafael
AU - Javier Ruiz-Pernía, José
AU - Tuñon, Iñaki
AU - Delgado, Eduardo J.
PY - 2019/2
Y1 - 2019/2
N2 - The effect of the protonation state of the hydroxyl-ethylthiamin diphosphate intermediate, HEThDP, on the enzyme-substrate interactions and their consequences on the biosynthesis of R-phenylacetylcarbinol, R-PAC, by the acetohydroxy acid synthase, AHAS, is addressed by molecular dynamics simulations. It is found that the form of HEThDP, which favors the formation of R-PAC, is that having the 4-aminopyrimidine ring with the N1′ atom protonated and the N4′ atom as aminopyrimidinium ion. Under this form both active sites of AHAS have the ability to perform the catalysis, unlike that observed for the other possible protonation states of N1′ and N4′ atoms.
AB - The effect of the protonation state of the hydroxyl-ethylthiamin diphosphate intermediate, HEThDP, on the enzyme-substrate interactions and their consequences on the biosynthesis of R-phenylacetylcarbinol, R-PAC, by the acetohydroxy acid synthase, AHAS, is addressed by molecular dynamics simulations. It is found that the form of HEThDP, which favors the formation of R-PAC, is that having the 4-aminopyrimidine ring with the N1′ atom protonated and the N4′ atom as aminopyrimidinium ion. Under this form both active sites of AHAS have the ability to perform the catalysis, unlike that observed for the other possible protonation states of N1′ and N4′ atoms.
UR - https://www.scopus.com/pages/publications/85059542835
U2 - 10.1016/j.cplett.2018.12.039
DO - 10.1016/j.cplett.2018.12.039
M3 - Article (Academic Journal)
AN - SCOPUS:85059542835
SN - 0009-2614
VL - 716
SP - 247
EP - 251
JO - Chemical Physics Letters
JF - Chemical Physics Letters
ER -