Substrate binding modifies the hinge bending characteristics of human 3-phosphoglycerate kinase: a molecular dynamics study.
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. 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 of the apo form indicate a hinge bending motion in the ns timescale while the time period of the hinge bending motion of the complex form is clearly over the 20 ns simulation time. The apo form exhibits several hinge points that contribute to the hinge bending motion while upon binding the ligands, the hinge bending becomes strictly restrained with one dominant hinge point in the vicinity of the substrates. At the same time, ligand binding results in an enhanced correlation of internal domain motions.
Department of Biophysics and Radiation Biology, Faculty of Medicine, Semmelweis University, Hungary.
Zoltan
Z
Palmai
Laurent
L
Chaloin
Corinne
C
Lionne
Judit
J
Fidy
David
D
Perahia
Erika
E
Balog
D001665:Binding Sites; D003198:Computer Simulation; D004163:Diphosphoglyceric Acids / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D010735:Phosphoglycerate Kinase / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000502:physiology*; D013816:Thermodynamics
D004163:Diphosphoglyceric Acids; D008024:Ligands; C015891:glycerate 1,3-biphosphate; D010735:Phosphoglycerate Kinase