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Enzymes work by solvation substitution rather than by desolvation
A Warshel1, J Aqvist, S Creighton
1Department of Chemistry, University of Southern California, Los Angeles, 90089-1062.
Summary
Enzymes do not create gas-phase environments. Instead, enzyme active sites offer specific polar environments that stabilize transition states, similar to solution but with lower activation barriers for reactions like amide hydrolysis.
Area of Science:
- Biochemistry
- Chemical Physics
- Enzymology
Background:
- The desolvation hypothesis suggests enzymes create gas-phase-like environments.
- This hypothesis posits that solvent displacement is key to enzymatic catalysis.
Purpose of the Study:
- To reexamine the desolvation hypothesis using a common energy reference.
- To analyze enzymatic reaction energetics in gas phase, solution, and active sites.
Main Methods:
- Defined a common reference energy for reactions in different environments.
- Used experimentally estimated solvation energies for amide hydrolysis.
- Analyzed reaction profiles in gas phase, solution, and enzyme active sites.
Main Results:
- Gas-phase amide hydrolysis has a very high activation barrier.
- Enzymatic and solution reactions show similar profiles with lower activation barriers.
- Enzyme active sites provide polar environments, not gas-phase-like ones.
Conclusions:
- Enzyme active sites stabilize ionic transition states electrostatically.
- Enzymes solvate transition states more effectively than water.
- The desolvation hypothesis is contradicted by thermodynamic analyses.