Transduction of enzyme-ligand binding energy into catalytic driving force.
We propose a testable general mechanism by which ligand binding energy can be used to drive a catalytic step in an enzyme catalyzed reaction or to do other forms of work involving protein molecules. This energy transduction theory is based on our finding of the widespread occurrence of ligand binding-induced protein macrostate interconversions each having a large invariant delta H0 accompanied by a small but highly variable delta G0. This phenomenon, which can be recognized by the large delta Cp0's it generates, can provide the necessary energy input step but is not in itself sufficient to constitute a workable transduction mechanism. A viable mechanism requires the additional presence of an 'energy transmission step' which is terminated to trigger the 'power' stroke at a precise location on the reaction coordinate, followed by an energetically inexpensive 'return' step to restore the machine to its initial conditions. In the model we propose here, these additional steps are provided by the existence of ligand inducible 2-state transitions in the free enzyme and in each of the enzyme complexes that occur along the reaction coordinate, and by the selective blocking of certain of these interconversions by high energetic barriers. We provide direct experimental evidence supporting the facts that these additional mechanistic components do exist and that the liver glutamate dehydrogenase reaction is indeed driven by just such machinery. We describe some aspects of the chemical nature of these transitions, and evidence for their occurrence in other systems.
Fisher
H F
HF
Department of Biochemistry, University of Kansas Medical Center, Kansas City, Missouri.
Singh
N
N
D000818:Animals; D002151:Calorimetry; D002384:Catalysis; D004798:Enzymes / Q000378:metabolism*; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008099:Liver / Q000201:enzymology; D008962:Models, Theoretical; D011485:Protein Binding; D013816:Thermodynamics
D004798:Enzymes; D008024:Ligands; D005969:Glutamate Dehydrogenase