The mechanism of inhibition of valyl-tRNA synthetase by S-adenosylhomocysteine.
S-Adenosylhomocysteine inhibits ATP-PPi exchange and tRNA aminoacylation reactions catalysed by pure lupin valyl-tRNA synthetase. The reactions catalysed by phenylalanyl-tRNA, tyrosyl-tRNA, seryl-tRNA, arginyl-tRNA and tryptophanyl-tRNA synthetases are not inhibited by S-adenosylhomocysteine. The inhibition is proportional to first power of S-adenosylhomocysteine concentration. S-Adenosylhomocysteine is a competitive inhibitor of the lupin valyl-tRNA synthetase with respect to ATP and valine in the ATP-PPi exchange reaction, noncompetitive with respect to ATP and valine and uncompetitive with respect to tRNA in the tRNA aminoacylation reaction. Inhibition constant for S-adenosylhomocysteine determined from the reciprocal of Km for tRNA vs. the inhibitor concentration (at saturating ATP and not saturating valine concentration) is 0.35 mM. Inhibition constants for S-adenosylhomocysteine determined from the ATP-PPi exchange are 0.21 mM at saturating valine concentration with variable ATP and 0.33 mM at saturating ATP concentration with variable valine. The data are consistent with the binding of S-adenosylhomocysteine to the valyl adenylate site on the enzyme.
D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors*; D006710:Homocysteine / Q000031:analogs & derivatives*; D007700:Kinetics; D012435:S-Adenosylhomocysteine / Q000494:pharmacology*; D012639:Seeds / Q000201:enzymology*; D013329:Structure-Activity Relationship; D014637:Valine-tRNA Ligase / Q000037:antagonists & inhibitors*
D006710:Homocysteine; D012435:S-Adenosylhomocysteine; D000604:Amino Acyl-tRNA Synthetases; D014637:Valine-tRNA Ligase