Substrate Binding Directs the Functional Hinge Bending Motion of Human 3-Phosphoglycerate Kinase

Abstract

3-Phosphogycerate kinase (PGK) is a two domain enzyme, with a binding site of the 1,3-bisphosphoglycerate on the N-domain and of the ADP on the C-domain. In order to transfer a phosphate group the enzyme has to undergo a hinge bending motion from open to closed conformation to bring the substrates to close proximity. Molecular dynamics simulation was used to elucidate the effect of ligand binding onto the domain motions of this enzyme. The simulation results indicate the presence of a relatively small amplitude hinge bending motion of ns timescale in the apo form while the time period of the hinge bending motion of the complex form is clearly over the 20 ns simulation time. Upon binding the ligands, the hinge bending shows more directed characteristics with one dominant hinge point in the vicinity of the substrates while the apo form exhibits several hinge points that contribute to the hinge bending motion. The correlation of interdomain atomic movements also increased upon substrates binding.