ARE BURIED SALT BRIDGES IMPORTANT FOR PROTEIN STABILITY AND CONFORMATIONAL SPECIFICITY

The side chains of Arg 31, Glu 36 and Arc 40 in Are repressor form a buried salt-bridge triad. The entire salt-bridge network can be replaced by hydrophobic residues in combinatorial randomization experiments resulting in active mutants that are significantly more stable than wild type. The crystal structure of one mutant reveals that the mutant side chains pack against each ether in an otherwise wild-type fold. Thus, simple hydrophobic interactions provide more stabilizing energy than the buried salt bridge and confer comparable conformational specificity.