Effect of a single amino acid substitution on stability of conformation of a protein

Abstract

THE role of individual amino acid residues in stabilising protein molecules is of interest, especially in connection with the mechanism of thermoresistance of thermophilic bacteria1 and in connection with the physicochemical basis of temperature sensitive mutants used widely in molecular biology studies. This problem has been approached mainly with the use of synthetic polypeptide2, chemical modification of natural proteins3, or homologous proteins4–9 from different species. Many mutants of microorganisms are available from genetic studies, however, in which the mutant proteins differ from wild type only at a single amino acid position. Such proteins often differ markedly in stability. We describe here a study of the α-subunit of tryptophan synthetase of Escherichia coli. The data suggest that the stability of a protein may be highly correlated with the hydrophobicity of the amino acid residues at some suitable positions. Further studies of this type may clarify the role of individual amino acid residues in stabilising proteins.