On the ionization state of the substrate in the active site of glutamate racemase. A QM/MM study about the importance of being zwitterionic.
Computer simulations on a QM/MM potential energy surface have been carried out to gain insights into the catalytic mechanism of glutamate racemase (MurI). Understanding such a mechanism is a challenging task from the chemical point of view because it involves the deprotonation of a low acidic proton by a relatively weak base to give a carbanionic intermediate. First, we have examined the dependency of the kinetics and thermodynamics of the racemization process catalyzed by MurI on the ionization state of the substrate (glutamate) main chain. Second, we have employed an energy decomposition procedure to study the medium effect on the enzyme-substrate electrostatic and polarization interactions along the reaction. Importantly, the present theoretical results quantitatively support the mechanistic proposal by Rios et al. [J. Am. Chem. Soc. 2000, 122, 9373-9385] for the PLP-independent amino acid racemases.
Puig
Eduard
E
Departament de Química, Universitat Autonoma de Barcelona, Bellaterra (Barcelona), Spain.
Garcia-Viloca
Mireia
M
González-Lafont
Angels
A
Lluch
José M
JM
D000591:Amino Acid Isomerases / Q000737:chemistry*; D001665:Binding Sites; D002384:Catalysis; D003198:Computer Simulation; D007477:Ions / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D011522:Protons; D055672:Static Electricity; D013816:Thermodynamics
D007477:Ions; D011522:Protons; D000591:Amino Acid Isomerases; C062292:glutamate racemase