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Updated: Jul 5, 2026
09:45
Measuring Protein Stability in Living Zebrafish Embryos Using Fluorescence Decay After Photoconversion (FDAP)
Published on: January 28, 2015
How protein stability and new functions trade off.
Nobuhiko Tokuriki1, Francois Stricher, Luis Serrano
1Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Plos Computational Biology
|May 9, 2008
Summary
Enzymatic evolution often reduces protein stability, but functional mutations are only slightly more destabilizing than average mutations. Compensatory, stabilizing mutations in non-functional regions are crucial for adapting enzyme activity.
Area of Science:
- Biochemistry
- Protein Engineering
- Evolutionary Biology
Background:
- Enzyme evolution frequently involves a trade-off between acquiring new functions and maintaining protein stability.
- Most mutations are destabilizing, raising questions about the nature of function-altering mutations.
Purpose of the Study:
- To compare the stability effects of function-altering mutations with all possible mutations in enzymes.
- To investigate how destabilizing effects of functional mutations are balanced during adaptation.
Main Methods:
- Utilized FoldX for DeltaDeltaG computations on 548 mutations from directed evolution of 22 enzymes.
- Compared stability effects, location, and type of function-altering mutations against all point mutations.
Main Results:
- Function-modulating mutations are largely destabilizing (average +0.9 kcal/mol), similar to average mutations (+1.3 kcal/mol).
- Mutations in substrate-binding pockets impose a greater stability cost than neutral surface mutations.
- Stabilizing mutations in non-critical regions often compensate for destabilizing functional mutations.
Conclusions:
- Enzyme evolution relies on a balance between destabilizing functional mutations and compensatory stabilizing mutations.
- Apparent 'silent' mutations play a vital role in enabling the adaptation of new enzymatic activities.
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