Lactate dehydrogenase from the tetraploid weatherfish Misgurnus fossilis during temperature adaptation: Determination of structural differences in two forms of the enzyme by molecular modeling methods

Abstract

A structural analysis of two lactate dehydrogenase M4 protein forms has been performed. These structures are the protein products of two lactate dehydrogenase gene (LDH-A) copies in the weatherfish Misgurnus fossilis genome after thermal adaptation (acclimation) to 5 degrees C and 18 degrees C. The localization of three earlier identified amino acid substitutions (Gly214Val, Leu304Ile, Asp312Glu) has been determined, and the molecular dynamics simulation and computer modeling of two forms of the enzyme from skeletal muscles LDH-M4 have been carried out. After molecular dynamics trajectory calculations carried out at 5, 18, and 25 degrees C, the intersubunit distances for all structures used in calculations have been determined. It has been found that the Gly214Val substitution localized in the intersubunit region leads to a new intersubunit interaction, which plays a role in the stabilization of tetrameric enzyme structure after the adaptation to 18 degrees C.