Energy Considerations Show that Low-Barrier Hydrogen Bonds do not Offer a Catalytic Advantage over Ordinary Hydrogen Bonds

Low-barrier hydrogen bonds have recently been proposed as a major factor in enzyme catalysis. Here we evaluate the feasibility of transition state (TS) stabilization by low-barrier hydrogen bonds in enzymes. Our analysis focuses on the facts that (i) a low-barrier hydrogen bond is less stable than a...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-11, Vol.93 (24), p.13665-13670
Main Authors: Warshel, Arieh, Papazyan, Arno
Format: Article
Language:English
Subjects:
Active sites
Binding Sites
Biochemistry
Biological Sciences
Catalysis
Electrostatics
Enzymes
Enzymes - chemistry
Enzymes - metabolism
Free energy
Hydrogen
Hydrogen Bonding
Hydrogen bonds
Kinetics
Models, Chemical
Models, Structural
Protons
Serine Endopeptidases - chemistry
Serine Endopeptidases - metabolism
Solvation
Solvents
Static Electricity
Thermodynamics
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Summary:Low-barrier hydrogen bonds have recently been proposed as a major factor in enzyme catalysis. Here we evaluate the feasibility of transition state (TS) stabilization by low-barrier hydrogen bonds in enzymes. Our analysis focuses on the facts that (i) a low-barrier hydrogen bond is less stable than a regular hydrogen bond in water, (ii) TSs are more stable in the enzyme active sites than in water, and (iii) a nonpolar active site would destabilize the TS relative to its energy in water. Combining these points and other experimental and theoretical facts in a physically consistent framework shows that a low-barrier hydrogen bond cannot stabilize the TS more than an ordinary hydrogen bond. The reason for the large catalytic effect of active site hydrogen bonds is that their formation entails a lower reorganization energy than their solution counterparts, due to the preorganized enzyme environment.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.24.13665