Submicromolar phosphinic inhibitors of Escherichia coli aspartate transcarbamoylase.
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.
Coudray
Laëtitia
L
Department of Chemistry, Texas Christian University, Box 298860, Fort Worth, TX 76129, USA.
Kantrowitz
Evan R
ER
Montchamp
Jean-Luc
JL
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
D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D010758:Phosphorus; D001224:Aspartic Acid; C013195:sparfosic acid; D001221:Aspartate Carbamoyltransferase; D010746:Phosphonoacetic Acid