Mutation of exposed hydrophobic amino acids to arginine to increase protein stability.
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.


CONCLUSIONS
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.
Strub
Caroline
C
Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France. caroline_strub@hotmail.com
Alies
Carole
C
Lougarre
Andrée
A
Ladurantie
Caroline
C
Czaplicki
Jerzy
J
Fournier
Didier
D
D000110:Acetylcholinesterase / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D000596:Amino Acids / Q000737:chemistry* / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000737:chemistry*; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D004795:Enzyme Stability / Q000235:genetics; D009154:Mutation / Q000235:genetics*
D000596:Amino Acids; D029721:Drosophila Proteins; D001120:Arginine; D000110:Acetylcholinesterase