TEMPERATURE-NEARLY-INDEPENDENT BINDING CONSTANT IN SEVERAL BIOCHEMICAL SYSTEMS - THE UNDERLYING ENTROPY-DRIVEN BINDING MECHANISM AND ITS PRACTICAL SIGNIFICANCE

Arguments are presented in this commentary to show that the model of t emperature-nearly-independent binding that we proposed to rationalize the binding characteristics of beta-adrenergic antagonists (Miklavc et al., Biochem Pharmacol 40: 663-669, 1990) in fact provides a consiste nt interpretation of the temperature-nearly-independent binding consta nt in all. other systems that have been reported in the literature: in the binding of coenzyme NADH to horse liver alcohol dehydrogenase and to octopine dehydrogenase and in the binding of an inhibitor to acety lcholinesterase. No such consistent interpretation has been given thus far for any of these systems. It is characteristic of them that the b inding takes place in a hydrophobic, sterically constrained environmen t. One can assume, therefore, that the underlying entropy-driven bindi ng mechanism would reflect the existence and the properties of the ste ric bottleneck surrounding the binding pocket. We also explain why the temperature effects characteristic of hydrophobic interactions are no t found experimentally in these systems, whereas in other, sometimes e ven structurally similar, systems such temperature effects are clearly present. Further work is necessary to establish more firmly the key f eatures of the temperature-nearly-independent binding mechanism that h as been disclosed through our analysis. The binding mechanism in quest ion not only appears in important biochemical systems, but also has th e interesting property of bring relatively unaffected by smaller struc tural changes.