Enzyme motions inside and out

Science

Volumn 312, Issue 5771, 2006, Pages 208-209

  Benkovic, Stephen J ^a   Hammes Schiffer, Sharon ^a  

^a PENNSYLVANIA STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ELECTRON ENERGY LEVELS; ELECTRON TUNNELING; HYDROGEN; NATURAL SCIENCES;

ENZYME MOTIONS; THERMAL MOTIONS; TRANSITIONS; TUNNELING;

ENZYMES;

HYDROGEN; OXIDOREDUCTASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; SCHIFF BASE; ARALKYLAMINE DEHYDROGENASE; PROTON; TRYPTAMINE; TRYPTAMINE DERIVATIVE;

ENZYME; ENZYME ACTIVITY; HYDROGEN; TEMPERATURE EFFECT;

CATALYSIS; ENERGY; ENZYME ACTIVITY; ENZYME CONFORMATION; ENZYME KINETICS; ENZYME MECHANISM; HEAT; NUCLEAR MAGNETIC RESONANCE; PHASE TRANSITION; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN TRANSPORT; PROTON TRANSPORT; REVIEW; TEMPERATURE DEPENDENCE; X RAY CRYSTALLOGRAPHY; BINDING SITE; CHEMICAL MODEL; CHEMISTRY; COMPUTER SIMULATION; KINETICS; METABOLISM; MOTION; NOTE; OXIDATION REDUCTION REACTION; PHYSICAL CHEMISTRY; PROTEIN CONFORMATION; THERMODYNAMICS;

BINDING SITES; CATALYSIS; CHEMISTRY, PHYSICAL; COMPUTER SIMULATION; HYDROGEN; KINETICS; MODELS, CHEMICAL; MOTION; OXIDATION-REDUCTION; OXIDOREDUCTASES ACTING ON CH-NH GROUP DONORS; PROTEIN CONFORMATION; PROTONS; THERMODYNAMICS; TRYPTAMINES;

EID: 33645836711     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1127654     Document Type: Review

References (17)

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13. In addition to changes in the average donor-acceptor distance, this mode vibrates on a relatively fast time scale due to thermal fluctuations, and it could be treated quantum mechanically. The dominant donor-acceptor distance for tunneling may differ for hydrogen and deuterium.
14. In the figure, the double-well proton potential becomes symmetric to enable hydrogen tunneling, but tunneling involving excited vibrational states is possible for an asymmetric proton potential.
15. This free-energy barrier is expected to be slightly higher for deuterium than for hydrogen because of zero point energy effects. If the reaction is adiabatic (that is, the system remains in the vibrational ground state), then this difference in free-energy barriers leads to a moderate kinetic isotope effect. If the reaction is vibrationally nonadiabatic (that is, excited vibrational states participate substantially), then the rate is approximately proportional to the square of the tunneling splitting, which is the energy difference between the lowest two vibrational states in the approximately symmetric double-well hydrogen potential at the top of the barrier. The smaller splitting for deuterium than for hydrogen can lead to a large kinetic isotope effect for these types of reactions. The reaction is assumed to occur in the ground electronic state.
16. Although the thermally averaged structures shown in the figure correspond to dihydrofolate reductase, here they represent a generic enzyme. The double-well potentials and associated quantum states are drawn qualitatively and will differ for each enzyme system.
17. This work was supported by NIH grant GM56207 (5.H.-5.) and GM24129 (S.J.B.).