TY - JOUR
T1 - Synthesis of cysteine-containing dipeptides by aminpacyl-tRNA synthetases
AU - Jakubowski, Hieronim
N1 - Funding Information: I thank Sylvain Blanquet, Gilbert Eriani and Paul Schimmel for plasmids. This research was supported by grants from the American Cancer Society (NP-904) and the National Science Foundation (MCB-9218358).
PY - 1995
Y1 - 1995
N2 - Arglnyl-tRNA synthetase (ArgRS) catalyses AMP- and PP1independent deacylation of Arg-tRNAArg9 in the presence of cysteine. A dipeptide, Arg-Cys, is a product of this deacylation reaction. Similar reaction with homocysteine yields Arg-Hcy. Arginine is a noncompetitive inhibitor of the cysteine-dependent deacylation which indicates that cysteine binds to the enzyme-Arg-tRNAArg.9 complex at a site separate from the arginine binding site. In the presence of arginine, [14C]Arg-tRNAArg is deacylated at a rate similar to the rate of its spontaneous deacylation in solution and [14C]arginine is a product. Experiments with cysteine derivatives indicate that the -SH group is essential for the reaction whereas -NH2 and -COOH groups are not. Thloesters of arginine are formed with 3-mercaptopropionic acid, N-acetyl-L-cysteine and dithiothreitol. These data suggest that formation of the dipeptide Arg-Cys involves a thioester intermediate, S->L-arginyl)- L-cysteine, which is not observed because of the rapid rearrangement to form a stable peptide bond. Facile intramolecular reaction results from the favorable geometric arrangement of the a-amino group of cysteine with respect to the thioester formed in the initial reaction. Similar reactions, yielding Ile-Cys and Val-Cys, are catalyzed by isoleucyl- and valyl-tRNA synthetases, respectively.
AB - Arglnyl-tRNA synthetase (ArgRS) catalyses AMP- and PP1independent deacylation of Arg-tRNAArg9 in the presence of cysteine. A dipeptide, Arg-Cys, is a product of this deacylation reaction. Similar reaction with homocysteine yields Arg-Hcy. Arginine is a noncompetitive inhibitor of the cysteine-dependent deacylation which indicates that cysteine binds to the enzyme-Arg-tRNAArg.9 complex at a site separate from the arginine binding site. In the presence of arginine, [14C]Arg-tRNAArg is deacylated at a rate similar to the rate of its spontaneous deacylation in solution and [14C]arginine is a product. Experiments with cysteine derivatives indicate that the -SH group is essential for the reaction whereas -NH2 and -COOH groups are not. Thloesters of arginine are formed with 3-mercaptopropionic acid, N-acetyl-L-cysteine and dithiothreitol. These data suggest that formation of the dipeptide Arg-Cys involves a thioester intermediate, S->L-arginyl)- L-cysteine, which is not observed because of the rapid rearrangement to form a stable peptide bond. Facile intramolecular reaction results from the favorable geometric arrangement of the a-amino group of cysteine with respect to the thioester formed in the initial reaction. Similar reactions, yielding Ile-Cys and Val-Cys, are catalyzed by isoleucyl- and valyl-tRNA synthetases, respectively.
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U2 - 10.1093/nar/23.22.4608
DO - 10.1093/nar/23.22.4608
M3 - Article
C2 - 8524650
SN - 0305-1048
VL - 23
SP - 4608
EP - 4615
JO - Nucleic acids research
JF - Nucleic acids research
IS - 22
ER -