title: Synthesis and binding of stable bisubstrate ligands for phosphoglycerate kinase.
abstract: Stable bisubstrate ligands of phosphoglycerate kinase (PGK) have been synthesized with AMP or ADP conjugated to hydrolytically-stable, symmetrical analogues of 1,3-bisphosphoglycerate and their binding to yeast PGK evaluated. Their Kds decrease with net negative charge, with a penta-anionic analogue 7 showing highest affinity-in accordance with its approximation to the transition state for the reaction catalysed by PGK.
authors.affiliation: Krebs Institute, Department of Chemistry, University of Sheffield, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Williams
authors.forename: D L
authors.initials: DL
authors.lastname: Jakeman
authors.forename: J S
authors.initials: JS
authors.lastname: Vyle
authors.forename: M P
authors.initials: MP
authors.lastname: Williamson
authors.forename: G M
authors.initials: GM
authors.lastname: Blackburn
mesh_terms: D000244:Adenosine Diphosphate / Q000031:analogs & derivatives*; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D004163:Diphosphoglyceric Acids / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010735:Phosphoglycerate Kinase / Q000378:metabolism*
chemical_list: D004163:Diphosphoglyceric Acids; D008024:Ligands; C015891:glycerate 1,3-biphosphate; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D010735:Phosphoglycerate Kinase