TY - JOUR
T1 - On the modulation of the substrate activity for the racemization catalyzed by mandelate racemase enzyme. A QM/MM study
AU - Prat-Resina, Xavier
AU - Garcia-Viloca, Mireia
AU - González-Lafont, Angels
AU - Lluch, José M.
PY - 2002/12/1
Y1 - 2002/12/1
N2 - A comparative QM/MM study of the racemization reaction of two different substrates of mandelate racemase, propargylglycolate and mandelate, has been carried out. The results have been compared with those previously obtained for vinylglycolate using the same methodology. The crucial point in understanding the catalytic activity seems to be the stabilization of the anionic intermediates in the active site. Our results indicate that there are at least three different mechanisms for the racemization. It is in the third mechanism, the most favorable one, where the modulation of the rate of racemization of β,γ-unsaturated α-hydroxycarboxylates by mandelate racemase is in accord with the experimental observations. Thus mandelate is the substrate that undergoes racemization by the enzyme at the highest rate. This is due to the highest efficiency of mandelate to delocalize the extra negative charge of the transition state and the intermediate that are found along the reaction path of the α-proton abstraction. The role of propargylglycolate as an inactivator of mandelate racemase has also been studied in comparison to its activity as a substrate of the enzyme.
AB - A comparative QM/MM study of the racemization reaction of two different substrates of mandelate racemase, propargylglycolate and mandelate, has been carried out. The results have been compared with those previously obtained for vinylglycolate using the same methodology. The crucial point in understanding the catalytic activity seems to be the stabilization of the anionic intermediates in the active site. Our results indicate that there are at least three different mechanisms for the racemization. It is in the third mechanism, the most favorable one, where the modulation of the rate of racemization of β,γ-unsaturated α-hydroxycarboxylates by mandelate racemase is in accord with the experimental observations. Thus mandelate is the substrate that undergoes racemization by the enzyme at the highest rate. This is due to the highest efficiency of mandelate to delocalize the extra negative charge of the transition state and the intermediate that are found along the reaction path of the α-proton abstraction. The role of propargylglycolate as an inactivator of mandelate racemase has also been studied in comparison to its activity as a substrate of the enzyme.
UR - http://www.scopus.com/inward/record.url?scp=0036979958&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036979958&partnerID=8YFLogxK
U2 - 10.1039/b204693h
DO - 10.1039/b204693h
M3 - Article
AN - SCOPUS:0036979958
SN - 1463-9076
VL - 4
SP - 5365
EP - 5371
JO - Physical Chemistry Chemical Physics
JF - Physical Chemistry Chemical Physics
IS - 21
ER -