Gly56 in the synthetic site of isoleucyl-tRNA synthetase confers specificity and maintains communication with the editing site.

Autor: Dulic M; Department of Chemistry, Faculty of Science, University of Zagreb, Croatia., Krpan N; Department of Chemistry, Faculty of Science, University of Zagreb, Croatia., Gruic-Sovulj I; Department of Chemistry, Faculty of Science, University of Zagreb, Croatia.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2023 Dec; Vol. 597 (24), pp. 3114-3124. Date of Electronic Publication: 2023 Dec 06.
DOI: 10.1002/1873-3468.14780
Abstrakt: Isoleucyl-tRNA synthetase (IleRS) links isoleucine to cognate tRNA via the Ile-AMP intermediate. Non-cognate valine is often mistakenly recognized as the IleRS substrate; therefore, to maintain the accuracy of translation, IleRS hydrolyzes Val-AMP within the synthetic site (pre-transfer editing). As this activity is not efficient enough, Val-tRNA Ile is formed and hydrolyzed in the distant post-transfer editing site. A strictly conserved synthetic site residue Gly56 was previously shown to safeguard Ile-to-Val discrimination during aminoacyl (aa)-AMP formation. Here, we show that the Gly56Ala variant lost its specificity in pre-transfer editing, confirming that this residue ensures the selectivity of all synthetic site reactions. Moreover, we found that the Gly56Ala mutation affects IleRS interaction with aa-tRNA likely by disturbing tRNA-dependent communication between the two active sites.
(© 2023 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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