Aminoacyl thioester chemistry of class II aminoacyl-tRNA synthetases

Hieronim Jakubowski

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60 Scopus citations


Lysyl-tRNA synthetase, a class II enzyme, edits homocysteine by converting it into homocysteine thiolactone. In a similar reaction, the enzyme converts homoserine into homoserine lactone. Other class II enzymes, aspartyl-tRNA synthetase and seryl-tRNA synthetase, do not edit any of the amino acids tested. However, all three class II aminoacyl-tRNA synthetases catalyze AMP- and pyrophosphate-independent deacylation of cognate aminoacyl- tRNA in the presence of thiols, mimicking editing of homocysteine. Thiol- dependent deacylations exhibit saturation kinetics with respect to concentration of thiols, suggesting the presence of a thiol binding site on each enzyme. 3-Mercaptopropionate-, N-acetyl-L-cysteine-, and dithiothreitol- dependent deacylations of aminoacyl-tRNA yield corresponding aminoacyl thioesters. Cysteine-dependent enzymatic deacylations of aminoacyl-tRNA by these class II enzymes yield dipeptides, N-(aminoacyl)cysteine. The formation of N-(aminoacyl)cysteine involves thioester intermediates S-(aminoacyl)-L- cysteine, which are not observed because of the facile transacylation of the aminoacyl residue from the sulfur to the α-amino group of cysteine to form a stable peptide bond. These data indicate that class II aminoacyl-tRNA synthetases possess unique thiol-binding subsites within their active sites. That the thiol-binding subsite exists also in AspRS and SerRS, which do not need editing function, suggests that these class II enzymes possess vestigial editing functions.

Original languageEnglish (US)
Pages (from-to)11077-11085
Number of pages9
Issue number37
StatePublished - Sep 16 1997

All Science Journal Classification (ASJC) codes

  • Biochemistry


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