Glycerol-3-Phosphate Dehydrogenase Isozymes: A computational approach to their metabolic roles in the flight muscles of triatoma infestans

Abstract

Glycerol-3-phosphate dehydrogenase (GPDH) isoenzymes play different roles in Triatoma infestans flight metabolism and only differ in the C-terminal end. We studied with computational models their dynamics and interactions. Homology-modeling dynamics showed models close to minimal energy with amino acid distribution similar to crystallized structures. Radius of gyration decrease because the models presented well fitted folded structures with solvation free energy of non-polar groups increased with temperature. Heat maps suggested the need to form dimeric structures to preserve activity or that temperature could be an activity modulator. Modeled dimeric structures were similar to crystallized references and didn´t involve the C-terminals in their conformation. Docking studies of the C-terminals showed interaction between GPDH-1 and actin co-localized with glycolytic enzymes. GPDH-2 peptide could bind to model membranes and be substrate for lysine-acetyltransferases. Consequently, C-terminals could determine the sub-cellular localization and the metabolic functions in lipid biosynthesis or ATP generation.