Coupling of hydrogenic tunneling to active-site motion in the hydrogen radical transfer catalyzed by a coenzyme B12-dependent mutase

Agnieszka Dybala-Defratyka, Piotr Paneth, Ruma Banerjee, Donald G. Truhlar

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

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 languageEnglish (US)
Pages (from-to)10774-10779
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number26
DOIs
StatePublished - Jun 26 2007

Keywords

  • Ensemble-averaged variational transition state theory
  • Enzyme kinetics
  • Kinetic isotope effects
  • Molecular modeling
  • Quantum dynamics

Fingerprint Dive into the research topics of 'Coupling of hydrogenic tunneling to active-site motion in the hydrogen radical transfer catalyzed by a coenzyme B<sub>12</sub>-dependent mutase'. Together they form a unique fingerprint.

Cite this