ArticleStructure (London, England : 1993)2012
Distinct states of methionyl-tRNA synthetase indicate inhibitor binding by conformational selection.
Article in Structure (London, England : 1993), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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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.
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Who cites it
46 citing papers in PubMed, 74 citations in OpenAlex.
- Discovery of a triple-site inhibitor targeting bacterial methionyl-tRNA synthetase through combined drug repurposing screening and generative AI-assisted optimization.Nucleic acids research · 2026Article
- ATP mimetics targeting prolyl-tRNA synthetases as a new avenue for antimalarial drug development.iScience · 2024Article
- CENsible: Interpretable Insights into Small-Molecule Binding with Context Explanation Networks.Journal of chemical information and modeling · 2024Article
- CENsible: Interpretable Insights into Small-Molecule Binding with Context Explanation Networks.bioRxiv : the preprint server for biology · 2023Article
- ExploringPharmaceuticals (Basel, Switzerland) · 2023Article
- Aminoacyl tRNA Synthetases: Implications of Structural Biology in Drug Development against Trypanosomatid Parasites.ACS omega · 2023Review
- Targeting prolyl-tRNA synthetase via a series of ATP-mimetics to accelerate drug discovery against toxoplasmosis.PLoS pathogens · 2023Article
- Double drugging of prolyl-tRNA synthetase provides a new paradigm for anti-infective drug development.PLoS pathogens · 2022Article
- Structural basis for the dynamics of human methionyl-tRNA synthetase in multi-tRNA synthetase complexes.Nucleic acids research · 2021Article
- Spontaneous Selection ofAntimicrobial agents and chemotherapy · 2021Article
- Aminoacyl-tRNA Synthetases as Valuable Targets for Antimicrobial Drug Discovery.International journal of molecular sciences · 2021Review
- Structure-guided discovery of selective methionyl-tRNA synthetase inhibitors with potent activity againstRSC medicinal chemistry · 2020Article
- Discovery of an Allosteric Binding Site in Kinetoplastid Methionyl-tRNA Synthetase.ACS infectious diseases · 2020Article
- Design, Synthesis, and Evaluation of Novel Anti-Trypanosomal Compounds.Tetrahedron · 2020Article
- Conformational heterogeneity in apo and drug-bound structures of Toxoplasma gondii prolyl-tRNA synthetase.Acta crystallographica. Section F, Structural biology communications · 2019Article
- Optimization of Methionyl tRNA-Synthetase Inhibitors for Treatment ofAntimicrobial agents and chemotherapy · 2019Article
- Aminoacyl tRNA synthetases as malarial drug targets: a comparative bioinformatics study.Malaria journal · 2019Article
- Article
- The crystal structure of the drug target Mycobacterium tuberculosis methionyl-tRNA synthetase in complex with a catalytic intermediate.Acta crystallographica. Section F, Structural biology communications · 2018Article
- Chemical Validation of Methionyl-tRNA Synthetase as a Druggable Target in Leishmania donovani.ACS infectious diseases · 2017Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
To guide development of new drugs targeting methionyl-tRNA synthetase (MetRS) for treatment of human African trypanosomiasis, crystal structure determinations of Trypanosoma brucei MetRS in complex with its substrate methionine and its intermediate product methionyl-adenylate were followed by those of the enzyme in complex with high-affinity aminoquinolone inhibitors via soaking experiments. Drastic changes in conformation of one of the two enzymes in the asymmetric unit allowed these inhibitors to occupy an enlarged methionine pocket and a new so-called auxiliary pocket. Interestingly, a small low-affinity compound caused the same conformational changes, removed the methionine without occupying the methionine pocket, and occupied the previously not existing auxiliary pocket. Analysis of these structures indicates that the binding of the inhibitors is the result of conformational selection, not induced fit.
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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.