The mechanism of lineage-specific tRNA recognition by bacterial tryptophanyl-tRNA synthetase and its implications for inhibitor discovery.

ABSTRACT: Tryptophanyl-tRNA synthetase (TrpRS) catalyzes the attachment of tryptophan (l-Trp) to tRNATrp, thereby providing the ribosome with a crucial substrate for the decoding of the UGG codon during protein translation. Both bacterial and eukaryotic TrpRSs are unable to efficiently cross-aminoacylate their respective tRNATrp substrates, indicating the evolution of lineage-specific mechanisms for tRNATrp recognition. Herein, we present the first co-crystal structure of bacterial TrpRS from Escherichia coli (EcTrpRS) in complex with its tRNATrp. EcTrpRS demonstrates bacterial-specific interactions with both the anticodon triplet and the acceptor arm of tRNATrp. Particularly, the bacterial-specific residue Glu155 forms hydrogen bonds with the discriminator base G73, thereby stabilizing it in a conf

SUBMITTER: Peng X 

PROVIDER: S-EPMC12135181 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature