Mutation of Exposed Hydrophobic Amino Acids to Arginine to Increase Protein Stability

Overview

Journal BMC Biochem

Publisher Biomed Central

Specialty Biochemistry

Date 2004 Jul 15

PMID 15251041

Citations 40

Authors

Caroline Strub

Carole Alies

Andree Lougarre

Caroline Ladurantie

Jerzy Czaplicki

Didier Fournier

Affiliations

Soon will be listed here.

Abstract

Background: One strategy to increase the stability of proteins is to reduce the area of water-accessible hydrophobic surface.

Results: In order to test it, we replaced 14 solvent-exposed hydrophobic residues of acetylcholinesterase by arginine. The stabilities of the resulting proteins were tested using denaturation by high temperature, organic solvents, urea and by proteolytic digestion.

Conclusion: Although the mutational effects were rather small, this strategy proved to be successful since half of the mutants showed an increased stability. This stability may originate from the suppression of unfavorable interactions of nonpolar residues with water or from addition of new hydrogen bonds with the solvent. Other mechanisms may also contribute to the increased stability observed with some mutants. For example, introduction of a charge at the surface of the protein may provide a new coulombic interaction on the protein surface.

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