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Amino acid analogues as substrates of a rabbit reticulocyte aminoacyl-tRNA synthetase preparation

1970; Elsevier BV; Volume: 2; Issue: 4 Linguagem: Inglês

10.1016/0009-2797(70)90056-6

1872-7786

S. Neale,

RNA modifications and cancer

l-Methionine-dependent ATP-PP1 exchange catalyzed by a partially purified aminoacyl-tRNA synthetase preparation from rabbit reticulocytes had a Km (methionine) of 0.2 mM. The amino acid analogues seleno-dl-methionine, α-methyl-dl-methionine, l-ethionine and seleno-dl-ethionine also promoted ATP-PP1 exchange, with Km values about 2- to 100-fold greater than that of methionine. A number of N-substituted derivatives of methionine were inactive as either substrates or inhibitors. Evidence is presented that methionyl-tRNA synthetase of rabbit reticulocytes can exist in different polymeric states. The best preparations obtained contained leucylvalyl and isoleucyl-tRNA synthetase activities. Using such preparations, phosphonic acid analogues of isoleucine, valine and leucine were shown, for the first time, to be specific inhibitors of the corresponding aminoacyl-tRNA synthetases. The inhibitory effects of l-methioninyl adenylate and l-leucinyl adenylate on norleucine-dependent ATP-PP1 exchange suggested that l-norleucine was a substrate of both methionyl- and leucyl-tRNA synthetases, a conclusion substantiated by heat denaturation studies and the fact that l-norleucine-dependent ATP-PP1 exchange was strongly inhibited by the phosphonic acid analogue of leucine.