ArticleProceedings of the National Academy of Sciences of the United States of America2010
Mechanistic insights into cognate substrate discrimination during proofreading in translation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 64 citations in OpenAlex.
- Indel-driven evolution of the canavanine tRNA-editing deacetylase enzyme CtdA.Journal of structural biology: X · 2025Article
- When Paul Berg meets Donald Crothers: an achiral connection through protein biosynthesis.Nucleic acids research · 2024Article
- Negative catalysis by the editing domain of class I aminoacyl-tRNA synthetases.Nucleic acids research · 2022Article
- Article
- Chiral checkpoints during protein biosynthesis.The Journal of biological chemistry · 2019Review
- A proof-reading mechanism for non-proteinogenic amino acid incorporation into glycopeptide antibiotics.Chemical science · 2019Article
- The Reverse Side of a Coin: "Factor-Free" Ribosomal Protein Synthesis In Vitro is a Consequence of the In Vivo Proofreading Mechanism.Biomolecules · 2019Article
- A chiral selectivity relaxed paralog of DTD for proofreading tRNA mischarging in Animalia.Nature communications · 2018Article
- Conformational and chemical selection by aProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Article
- Discovery and Investigation of Natural Editing Function against Artificial Amino Acids in Protein Translation.ACS central science · 2017Article
- Cryptosporidium and Toxoplasma Parasites Are Inhibited by a Benzoxaborole Targeting Leucyl-tRNA Synthetase.Antimicrobial agents and chemotherapy · 2016Article
- 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
- Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification.Life (Basel, Switzerland) · 2015Review
- Expanding a tyrosyl-tRNA synthetase assay to other aminoacyl-tRNA synthetases.Data in brief · 2015Article
- Specificity and catalysis hardwired at the RNA-protein interface in a translational proofreading enzyme.Nature communications · 2015Article
- Universal pathway for posttransfer editing reactions: insights from the crystal structure of TtPheRS with puromycin.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Article
- Thermodynamic properties distinguish human mitochondrial aspartyl-tRNA synthetase from bacterial homolog with same 3D architecture.Nucleic acids research · 2013Article
- Translational fidelity maintenance preventing Ser mis-incorporation at Thr codon in protein from eukaryote.Nucleic acids research · 2013Article
Corrections and comments
- Commented on by
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Editing/proofreading by aminoacyl-tRNA synthetases is an important quality control step in the accurate translation of the genetic code that removes noncognate amino acids attached to tRNA. Defects in the process of editing result in disease conditions including neurodegeneration. While proofreading, the cognate amino acids larger by a methyl group are generally thought to be sterically rejected by the editing modules as envisaged by the "Double-Sieve Model." Strikingly using solution based direct binding studies, NMR-heteronuclear single quantum coherence (HSQC) and isothermal titration calorimetry experiments, with an editing domain of threonyl-tRNA synthetase, we show that the cognate substrate can gain access and bind to the editing pocket. High-resolution crystal structural analyses reveal that functional positioning of substrates rather than steric exclusion is the key for the mechanism of discrimination. A strategically positioned "catalytic water" molecule is excluded to avoid hydrolysis of the cognate substrate using a "RNA mediated substrate-assisted catalysis mechanism" at the editing site. The mechanistic proof of the critical role of RNA in proofreading activity is a completely unique solution to the problem of cognate-noncognate selection mechanism.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.