title: Computational simulation of ligand docking to L-type pyruvate kinase subunit.
abstract: Computational blind docking approach was used for mapping of possible binding sites in L-type pyruvate kinase subunit for peptides, RRASVA and the phosphorylated derivative RRAS(Pi)VA, which model the phosphorylatable N-terminal regulatory domain of the enzyme. In parallel, the same docking analysis was done for both substrates of this enzyme, phosphoenolpyruvate (PEP) and adenosine diphosphate (ADP), and for docking of fructose 1,6-bisphosphate (FBP), which is the allosteric activator of the enzyme. The binding properties of the entire surface of the protein were scanned and several possible binding sites were identified in domains A and C of the protein, while domain B revealed no docking sites for peptides or for substrates or the allosteric regulator. It was found that the docking sites of different ligands were partially overlapping, pointing to the possibility that some regulatory effects, observed in the case of L-type pyruvate kinase, may be caused by the competition of different ligands for the same binding sites.
authors: Institute of Chemistry, University of Tartu, Ravila 14A, 50411 Tartu, Estonia.
authors: Aleksei
authors: A
authors: Kuznetsov
authors: Institute of Chemistry, University of Tartu, Ravila 14A, 50411 Tartu, Estonia.
authors: Ilona
authors: I
authors: Faustova
authors: Institute of Chemistry, University of Tartu, Ravila 14A, 50411 Tartu, Estonia. Electronic address: jaak.jarv@ut.ee.
authors: Jaak
authors: J
authors: Järv
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D001665:Binding Sites; D003198:Computer Simulation; D005635:Fructosediphosphates / Q000737:chemistry; D008024:Ligands; D062105:Molecular Docking Simulation; D010455:Peptides / Q000737:chemistry; D010728:Phosphoenolpyruvate / Q000737:chemistry; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D011770:Pyruvate Kinase / Q000737:chemistry*
chemical_list: D005635:Fructosediphosphates; D008024:Ligands; D010455:Peptides; D021122:Protein Subunits; D000244:Adenosine Diphosphate; D010728:Phosphoenolpyruvate; D011770:Pyruvate Kinase; C029063:fructose-1,6-diphosphate
keywords: L-type pyruvate kinase; N-terminal domain docking in protein; Putative N-terminal docking sites; Regulatory phosphorylation; Substrate affinity regulation; Switching in cooperativity