Fitness of enzyme binding sites for their physical environment: Coenzyme and substrate binding sites of M4 lactate dehydrogenases

Abstract

1.1. At the adenosine subsite of the coenzyme binding region of M4 lactate dehydrogenase, the hydrophobic contribution to binding is strongly disrupted at low temperatures and high pressures.2.2. Animals living in different thermal regimes circumvent this problem by adjusting the enthalphy, entropy, volume changes associated with binding.3.3. An extreme example of this adaptational strategy is supplied by M4 lactate dehydrogenase from an abyssal organism (Antimora rostrata) living at 2°C and up to several hundred atmospheres of pressure.4.4. Antimora M4 lactate dehydrogenase appears to have a smaller hydrophobic region in the coenzyme binding site, playing a measurably reduced role in ligand binding.5.5. In contrast, alternative non-covalent contributions to binding substrate and substrate analogue are stabilized at low temperatures and high pressures, and as a consequence, the enthalpy, entropy, and volume changes occurring during substrate binding by lactate dehydrogenase from the abyssal organism also can be much reduced compared to the mammalian homologue.