ArticleThe Journal of biological chemistry2012
Substrate specificity of bacterial prolyl-tRNA synthetase editing domain is controlled by a tunable hydrophobic pocket.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Inhibition of prolyl-tRNA synthetase and efflux pumps as a dual-targeting strategy against multidrug-resistant bacteria.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Mechanistic and evolutionary insights into a family of aminoacyl-tRNA deacylases that protects against canavanine toxicity.Nucleic acids research · 2025Article
- Structural basis of tRNAPro acceptor stem recognition by a bacterial trans-editing domain.Nucleic acids research · 2023Article
- Amino Acid Specificity of Ancestral Aminoacyl-tRNA Synthetase Prior to the Last Universal Common Ancestor Commonote commonote.Journal of molecular evolution · 2022Article
- Effect of Charge Distribution in a Modified tRNA Substrate on Pre-Reaction Protein-tRNA Complex Geometry.ACS omega · 2021Article
- Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement.Beilstein journal of organic chemistry · 2021Review
- HumanThe Journal of biological chemistry · 2020Article
- Article
- Quality control by trans-editing factor prevents global mistranslation of non-protein amino acid α-aminobutyrate.RNA biology · 2018Article
- Conformational and chemical selection by aProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Elongation Factor Tu Prevents Misediting of Gly-tRNA(Gly) Caused by the Design Behind the Chiral Proofreading Site of D-Aminoacyl-tRNA Deacylase.PLoS biology · 2016Article
- Essentiality Assessment of Cysteinyl and Lysyl-tRNA Synthetases of Mycobacterium smegmatis.PloS one · 2016Article
- Specificity and catalysis hardwired at the RNA-protein interface in a translational proofreading enzyme.Nature communications · 2015Article
- Strictly conserved lysine of prolyl-tRNA Synthetase editing domain facilitates binding and positioning of misacylated tRNA(Pro.).Biochemistry · 2014Article
- A multiple aminoacyl-tRNA synthetase complex that enhances tRNA-aminoacylation in African trypanosomes.Molecular and cellular biology · 2013Article
- Exclusive use of trans-editing domains prevents proline mistranslation.The Journal of biological chemistry · 2013Article
- Aminoacyl-tRNA substrate and enzyme backbone atoms contribute to translational quality control by YbaK.The journal of physical chemistry. B · 2013Article
- Kinetic partitioning between synthetic and editing pathways in class I aminoacyl-tRNA synthetases occurs at both pre-transfer and post-transfer hydrolytic steps.The Journal of biological chemistry · 2012Article
- Substrate and enzyme functional groups contribute to translational quality control by bacterial prolyl-tRNA synthetase.The journal of physical chemistry. B · 2012Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Aminoacyl-tRNA synthetases catalyze the covalent attachment of amino acids onto their cognate tRNAs. High fidelity in this reaction is crucial to the accurate decoding of genetic information and is ensured, in part, by proofreading of the newly synthesized aminoacyl-tRNAs. Prolyl-tRNA synthetases (ProRS) mischarge tRNA(Pro) with alanine or cysteine due to their smaller or similar sizes relative to cognate proline. Mischarged Ala-tRNA(Pro) is hydrolyzed by an editing domain (INS) present in most bacterial ProRSs. In contrast, the INS domain is unable to deacylate Cys-tRNA(Pro), which is hydrolyzed exclusively by a freestanding trans-editing domain known as YbaK. Here, we have used computational and experimental approaches to probe the molecular basis of INS domain alanine specificity. We show that the methyl side chain of alanine binds in a well defined hydrophobic pocket characterized by conserved residues Ile-263, Leu-266, and Lys-279 and partially conserved residue Thr-277 in Escherichia coli ProRS. Site-specific mutation of these residues leads to a significant loss in Ala-tRNA(Pro) hydrolysis, and altering the size of the pocket modulates the substrate specificity. Remarkably, one ProRS INS domain variant displays a complete switch in substrate specificity from alanine to cysteine. The mutually exclusive aminoacyl-tRNA substrate specificities of the WT and engineered INS domains is consistent with the evolution of two distinct editing domains that function to clear Ala-tRNA(Pro) and Cys-tRNA(Pro) in vivo.
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