Enabling Role of Ligand-Driven Conformational Changes in Enzyme Evolution.

ABSTRACT: Many enzymes that show a large specificity in binding the enzymatic transition state with a higher affinity than the substrate utilize substrate binding energy to drive protein conformational changes to form caged substrate complexes. These protein cages provide strong stabilization of enzymatic transition states. Using part of the substrate binding energy to drive the protein conformational change avoids a similar strong stabilization of the Michaelis complex and irreversible ligand binding. A seminal step in the development of modern enzyme catalysts was the evolution of enzymes that couple substrate binding to a conformational change. These include enzymes that function in glycolysis (triosephosphate isomerase), the biosynthesis of lipids (glycerol phosphate dehydrogenase), the hexose m

SUBMITTER: Richard JP 

PROVIDER: S-EPMC9354746 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature