ArticleThe Journal of biological chemistry2016
Selective Inhibition of Bacterial Tryptophanyl-tRNA Synthetases by Indolmycin Is Mechanism-based.
Article in The Journal of biological chemistry, 2016. 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, 52 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
- Atomic-Level Structures Reveal How a Repurposed 3‑Aminopyrazine-2-carboxamide Scaffold InhibitsACS omega · 2026Article
- Multi-omics uncovers the critical role of ceramide-mediatedJournal of pharmaceutical analysis · 2026Article
- Therapeutic Potential of Isoxazole-(Iso)oxazole Hybrids: Three Decades of Research.International journal of molecular sciences · 2025Review
- The mechanism of lineage-specific tRNA recognition by bacterial tryptophanyl-tRNA synthetase and its implications for inhibitor discovery.Nucleic acids research · 2025Article
- The crystal structures of apo and tryptophan-bound tryptophanyl-tRNA synthetase from Neisseria gonorrhoeae.Acta crystallographica. Section F, Structural biology communications · 2025Article
- Functional analysis of the novel mitochondrial tRNAWorld journal of diabetes · 2024Article
- Specific glycine-dependent enzyme motion determines the potency of conformation selective inhibitors of threonyl-tRNA synthetase.Communications biology · 2024Article
- An asymmetric structure of bacterial TrpRS supports the half-of-the-sites catalytic mechanism and facilitates antimicrobial screening.Nucleic acids research · 2023Article
- Partitioning of the initial catalytic steps of leucyl-tRNA synthetase is driven by an active site peptide-plane flip.Communications biology · 2022Article
- Fibrivirga algicola gen. nov., sp. nov., an algicidal bacterium isolated from a freshwater river.Antonie van Leeuwenhoek · 2022Article
- Thermofluor-Based Analysis of Protein Integrity and Ligand Interactions.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Inhibition of Isoleucyl-tRNA Synthetase by the Hybrid Antibiotic Thiomarinol.Journal of the American Chemical Society · 2021Article
- Natural Trojan horse inhibitors of aminoacyl-tRNA synthetases.RSC chemical biology · 2021Review
- Aminoacyl-tRNA Synthetases as Valuable Targets for Antimicrobial Drug Discovery.International journal of molecular sciences · 2021Review
- Multi 'Omics Analysis of Intestinal Tissue in Ankylosing Spondylitis Identifies Alterations in the Tryptophan Metabolism Pathway.Frontiers in immunology · 2021Article
- The iron-dependent repressor YtgR is a tryptophan-dependent attenuator of the trpRBA operon in Chlamydia trachomatis.Nature communications · 2020Article
- Design and synthesis of novel spirooxindole-indenoquinoxaline derivatives as novel tryptophanyl-tRNA synthetase inhibitors.Molecular diversity · 2020Article
- Escapement mechanisms: Efficient free energy transduction by reciprocally-coupled gating.Proteins · 2020Article
- Antioxidant activity and antibacterial evaluation of new thiazolin-4-one derivatives as potential tryptophanyl-tRNA synthetase inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Indolmycin is a natural tryptophan analog that competes with tryptophan for binding to tryptophanyl-tRNA synthetase (TrpRS) enzymes. Bacterial and eukaryotic cytosolic TrpRSs have comparable affinities for tryptophan (Km ∼ 2 μm), and yet only bacterial TrpRSs are inhibited by indolmycin. Despite the similarity between these ligands, Bacillus stearothermophilus (Bs)TrpRS preferentially binds indolmycin ∼1500-fold more tightly than its tryptophan substrate. Kinetic characterization and crystallographic analysis of BsTrpRS allowed us to probe novel aspects of indolmycin inhibitory action. Previous work had revealed that long range coupling to residues within an allosteric region called the D1 switch of BsTrpRS positions the Mg(2+) ion in a manner that allows it to assist in transition state stabilization. The Mg(2+) ion in the inhibited complex forms significantly closer contacts with non-bridging oxygen atoms from each phosphate group of ATP and three water molecules than occur in the (presumably catalytically competent) pre-transition state (preTS) crystal structures. We propose that this altered coordination stabilizes a ground state Mg(2+)·ATP configuration, accounting for the high affinity inhibition of BsTrpRS by indolmycin. Conversely, both the ATP configuration and Mg(2+) coordination in the human cytosolic (Hc)TrpRS preTS structure differ greatly from the BsTrpRS preTS structure. The effect of these differences is that catalysis occurs via a different transition state stabilization mechanism in HcTrpRS with a yet-to-be determined role for Mg(2+). Modeling indolmycin into the tryptophan binding site points to steric hindrance and an inability to retain the interactions used for tryptophan substrate recognition as causes for the 1000-fold weaker indolmycin affinity to HcTrpRS.
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.