Contributions of individual amino acid residues to the structural stability of cetacean myoblobins

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Abstract
The acid-denaturation behavior of 11 cetacean myoglobins (Mb) was studied at 2 ionic strengths, 0.01 and 0.10 M, at 25.0.degree. C. The Mb studied fall into 4 phylogenetic suborders, representing the sperm whales, dolphins, baleen whales, and beaked whales. The differences in response to acid denaturation among these closely related Mb are small but statistically significant. In 3 cases, free-energy differences between Mb can be ascribed to 1 amino acid difference and in 3 others to 2 differences. The differences in response were analyzed in terms of the changes in noncovalent interactions occurring in the native structure. The effects of changes in electrostatic interactions over the whole charge array were calculated for each Mb species by using the modified Tanford-Kirkwood theory. The predicted changes in stability correlated well with the experimental observations in most cases. When differences in H-bonding capability were considered at a first approximation, substantial effects were predicted. When these effects were taken in conjunction with the electrostatic interactions, the correlation with experiment was improved. Additionally, restrictions in motional freedom and packing constraints appeared to be significant in the single-site analysis. The detectable differences in stability due to single amino acid substitutions along with the small differences in stability between the cetacean suborders indicate that compensatory interactions provide the mechanism for the conservation of stability among the Mb studied.