Inhibition of amino acyl tRNA synthetase activity by copper complexes of two metal binding ligands. N-Methyl isatin beta-thiosemicarbazone and 8-hydroxyquinoline.
Copper complexes of N-methyl isatin beta-thiosemicarbazone, 1-formyl isoquinoline thiosemicarbazone and thiosemicarbazide inhibit amino acyl tRNA synthetase activity. Copper complexes of 8-hydroxyquinoline and 8-mercaptoquinoline also inhibit. The 1 : 1 ligand-metal complex is significantly more active than the 2 : 1 complex. The free ligand alone and copper sulfate alone have little, if any, effect. These complexes have no effect on the ATP-PPi exchange reaction and do not cause deacylation of amino acyl tRNAs. This indicates that the process inhibited by these complexes is the amino acylation reaction. This is the first report that these copper binding ligands can inhibit enzymatic processes which involve nucleic acids but which are not viral, bacterial or mammalian cell polymerases.
D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors*; D000818:Animals; D002645:Chickens; D003300:Copper / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D006912:Hydroxyquinolines / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008720:Methisazone / Q000494:pharmacology*; D015125:Oxyquinoline / Q000494:pharmacology*; D013882:Thiosemicarbazones / Q000494:pharmacology*
D006912:Hydroxyquinolines; D013882:Thiosemicarbazones; D015125:Oxyquinoline; D003300:Copper; D000604:Amino Acyl-tRNA Synthetases; D008720:Methisazone