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Low-barrier hydrogen bonds and enzymatic catalysis
1Institute for Enzyme Research and Department of Biochemistry, University of Wisconsin, Madison 53705, USA. cleland@enzyme.wisc.edu
Archives of Biochemistry and Biophysics
|October 29, 2000
Summary
Low-barrier hydrogen bonds form when atoms sharing a proton have similar pK values, strengthening enzyme catalysis. Matching pK values significantly enhance binding affinity, as seen in serine proteases.
Area of Science:
- Biochemistry
- Chemical Physics
Background:
- Hydrogen bonds are crucial in biological systems.
- Low-barrier hydrogen bonds (LBHBs) are a specific type with unique properties.
Purpose of the Study:
- To define the characteristics of LBHBs.
- To explore their role in enzyme catalysis and binding affinity.
Main Methods:
- Analysis of hydrogen bond properties (distance, fractionation factor, NMR chemical shift).
- Thermodynamic analysis of hydrogen bond strength (deltaH).
- Case study of serine proteases and trifluoromethyl ketone inhibitors.
Main Results:
- LBHBs occur when pK values of participating atoms are similar, with distances ≤ 2.5 Å.
- Deuterium substitution leads to a deuterium fractionation factor < 0.5 and up-field NMR shifts.
- LBHBs can significantly increase binding strength (e.g., five orders of magnitude in serine proteases).
Conclusions:
- Matching pK values are key to forming strong LBHBs.
- LBHBs contribute significantly to enzyme catalytic efficiency.
- These bonds are likely prevalent in transition states of acid-base catalyzed reactions.