Combining thermostable mutations increases the stability of .lambda. repressor

Abstract
We have combined three mutations previously shown to stabilize .lambda. repressor agaisnt thermal denaturation. Two of these mutations are in helix 3, where Gly-46 and Gly-48 have been replaced by alanines [Hecht, M.H., et al. (1986) Proteins: Struct., Funct., Genet. 1, 43-46]. THe other mutation, which replaces Tyr-88 with cysteine, allows the protein to form an intersubunit disulfide bond [Sauer, R. T., et al. (1986) Biochemistry 25, 5992-5998]. Calorimetric measurements show that the two alanine substitutions stablize repressor by about 8.degree. C, that the disulfide bond stabilizes repressor by about 8.degree. C, and that the triple mutant is 16.degree. more stable than wild-type repressor.