Temperature as a selective factor in protein evolution: the adaptational strategy of "compromise".

Most of the important functional and structural properties of enzymes are affected by temperature. In order to maintain critical enzymic properties such as regulatory sensitivity, catalytic potential and structural stability, significant changes have been made in enzymes during evolution in different thermal regimes. Regulatory function, as typified by substrate binding ability, has been especially conservative. For a given enzyme, substrate binding ability is maintained at a relatively stable level over the entire temperature range experienced by the organism (enzyme), in spite of wide variation in substrate affinity at temperatures outside the biological range. Similarities in substrate affinity among homologues and analogues of enzymes from bacteria, invertebrates, fishes and mammals, at respective physiological temperatures for the enzymes, demonstrate the crucial importance of regulatory abilities in enzymes. Two facts, (a) that enzymes function at sub-maximal rates, and (b) that low temperature compensation is not effected by wholesale reductions in apparent Km values, argue that regulation outweighs sheer catalytic potential in enzymic function. The efficiency of an enzyme to catalyze a reaction at a rapid rate appears highest in low cell-temperature forms. The finding that catalytic efficiency is inversely correlated with enzymic heat stability suggests that enzymes with relatively great abilities to undergo conformational changes during catalysis are capable of supplying the most energy for activation events, this energy arising in part from the exergonic formation of weak bonds during the activation step in catalysis. Energy changes due to conformational changes may also be used to reduce the net enthalpy change which occurs during ligand binding, a mechanism we refer to as "coupled-compensating enthalpy changes." Comparisons of amino acid compositions of enzyme homologues and analogues from differently thermally adapted species do not reveal major differences, for example, in the overall hydrophobicity of enzymes. We propose that observed differences in enzyme thermal stability derive more from quantitative differences, i.e., differences in total numbers of secondary interactions, than from quilitative differences, i.e., differences in the relative importance of different classes of weak bonds.