Correlations between tertiary structure and energetics of coenzyme binding in pig heart muscle lactate dehydrogenase

Fluorescence, equilibrium dialysis, and microcalorimetric measurements have been performed on complex formation between pig heart muscle lactate dehydrogenase (EC 1.1.1.27) and a series of systematically modified nicotinamide adenine dinucleotide analogues to provide quantitative data for a discussion on energy-structure-function correlations. As a result of these studies, one can draw the conclusion that estimates of the relative stability of enzyme-ligand complexes on the mere basis of structural information on the macromolecule and its complexes with the ligand are likely to neglect contributions to the energy and entropy parameters, which stem from such processes as changes in solvation and conformation of both the free ligand and the macromolecule in the reaction. Since the reaction parameters reflect the differences between these states, information on hydrogen bonding and hydrophobic interaction schemes of the liganded and unliganded macromolecule alone is principally insufficient.