title: Inhibition of carbamyl phosphate synthetase by P1, P5-di(adenosine 5')-pentaphosphate: evidence for two ATP binding sites.
abstract: Studies on the effect of a series of alpha, omega-diadenosine 5'-polyphosphate (ApnA; n = 2 to 6) on carbamyl phosphate synthetase showed that only Ap5A is an effective inhibitor. Ap5A also inhibits two partial reactions catalyzed by the enzyme: bicarbonate-dependent ATPase and ATP synthesis from carbamyl phosphate and ADP. The data indicate that Ap5A binds to the enzyme sites that interact with ATP. Of a variety of ATP-utilizing enzymes (kinases, hydrolases, synthetases), only adenylate kinase (Leinhard, G. E., and Secemski, I. I. (1973) J. Biol. Chem. 248, 1121--1123) and carbamyl phosphate synthetase are inhibited by Ap5A. The present findings provide strong evidence that carbamyl phosphate synthetase has two separate binding sites for ATP in which the gamma-phosphate moeities of ATP are bound in close proximity to the bicarbonate binding site of the enzyme.
mesh_terms: D000227:Adenine Nucleotides / Q000494:pharmacology*; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007292:Inosine Nucleotides / Q000494:pharmacology; D009841:Oligonucleotides / Q000494:pharmacology*; D009843:Oligoribonucleotides / Q000494:pharmacology*; D009952:Ornithine / Q000494:pharmacology; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000227:Adenine Nucleotides; D007292:Inosine Nucleotides; D009841:Oligonucleotides; D009843:Oligoribonucleotides; D000255:Adenosine Triphosphate; D009952:Ornithine; D010770:Phosphotransferases; D000251:Adenosine Triphosphatases; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)