Abstract
Hydrogen transfer reactions catalyzed by coenzyme B12-dependent methylmalonyl-CoA mutase have very large kinetic isotope effects, indicating that they proceed by a highly quantal tunneling mechanism. We explain the kinetic isotope effect by using a combined quantum mechanical/molecular mechanical potential and semiclassical quantum dynamics calculations. Multidimensional tunneling increases the magnitude of the calculated intrinsic hydrogen kinetic isotope effect by a factor of 3.6 from 14 to 51, in excellent agreement with experimental results. These calculations confirm that tunneling contributions can be large enough to explain even a kinetic isotope effect >50, not because the barrier is unusually thin but because corner-cutting tunneling decreases the distance over which the system tunnels without a comparable increase in either the effective potential barrier or the effective mass for tunneling.
Original language | English (US) |
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Pages (from-to) | 10774-10779 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 104 |
Issue number | 26 |
DOIs | |
State | Published - Jun 26 2007 |
Keywords
- Ensemble-averaged variational transition state theory
- Enzyme kinetics
- Kinetic isotope effects
- Molecular modeling
- Quantum dynamics