Structural distribution of stability in a thermophilic enzyme

Stability parameters for individual residues in Thermus thermophilus cystei ne-free RNase H were determined by native state hydrogen exchange, thus pro viding a unique comparison of regional thermodynamics between thermophilic and mesophilic homologues. The general distribution of stability in the the rmophilic protein is similar to that of its mesophilic homologue, with a pr oportional increase in stability for almost an residues. As a consequence, the residue-specific stabilities of the two proteins are remarkably similar under conditions where their global stabilities are the same. These result s indicate that T. thermophilus RNase H is stabilized in a delocalized fash ion, preserving a finely tuned balance of stabilizing interactions througho ut the structure. Therefore, although protein stability can be altered by s ingle amino acid substitution, evolution for optimal function may require m ore subtle and delocalized mechanisms.