title: Submicromolar phosphinic inhibitors of Escherichia coli aspartate transcarbamoylase.
abstract: The design, syntheses, and enzymatic activity of two submicromolar competitive inhibitors of aspartate transcarbamoylase (ATCase) are described. The phosphinate inhibitors are analogs of N-phosphonacetyl-l-aspartate (PALA) but have a reduced charge at the phosphorus moiety. The mechanistic implications are discussed in terms of a possible cyclic transition-state during enzymatic catalysis.
authors.affiliation: Department of Chemistry, Texas Christian University, Box 298860, Fort Worth, TX 76129, USA.
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Coudray
authors.forename: Evan R
authors.initials: ER
authors.lastname: Kantrowitz
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Montchamp
mesh_terms: D001221:Aspartate Carbamoyltransferase / Q000737:chemistry*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D001667:Binding, Competitive; D002384:Catalysis; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003124:Colorimetry / Q000379:methods; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D010758:Phosphorus / Q000737:chemistry; D011487:Protein Conformation
chemical_list: D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D010758:Phosphorus; D001224:Aspartic Acid; C013195:sparfosic acid; D001221:Aspartate Carbamoyltransferase; D010746:Phosphonoacetic Acid