화학공학소재연구정보센터
Journal of the American Chemical Society, Vol.123, No.51, 12837-12848, 2001
An alternative explanation for the catalytic proficiency of orotidine 5'-phosphate decarboxylase
Orotidine 5'-phosphate decarboxylase (ODCase) is the most proficient enzyme known, enhancing the rate of decarboxylation of orotidine 5'-phosphate (OMP) by a factor of 10(17), which corresponds to a Delta DeltaG(double dagger) of similar to 24 kcal/mol. Ground-state destabilization through local electrostatic stress has been recently proposed as the basis of catalytic rate enhancement for a mechanism that is the same as in solution. We have carried out gas-phase ab initio quantum mechanical calculations combined with a free energy method, a continuum solvent model, and molecular dynamics simulations to assess an alternative mechanism. Although we are not able to reproduce the experimentally observed Delta DeltaG(double dagger) quantitatively, we present evidence that this Delta DeltaG(double dagger) is very large, in the range found experimentally. We thus conclude that the preferred mechanism may well be different from that in solution, involving an equilibrium pre-protonation of OMP C5 by a catalytic lysine residue that greatly reduces the barrier to subsequent decarboxylation.