STRUCTURAL DETERMINANTS OF THE STABILITY OF THERMOLYSIN-LIKE PROTEINASES

Thermolysin is a member of a family of homologous proteinases which di ffer in their resistance to thermally induced unfolding and subsequent autolytic degradation. Site-directed mutagenesis studies of the therm olysin-like proteinase (TLP) from Bacillus stearothermophilus (TLP-ste ) show that its reduced resistance to thermally induced autolysis, as compared to thermolysin, is due to only some of the 44 naturally occur ring amino-acid differences between them. in fact TLP-ste becomes more resistant than thermolysin by mutation of just a few of these amino-a cids. The crucial differences are all localized to a solvent-exposed r egion in the N-terminal domain of TLP-ste.