ArticleScience (New York, N.Y.)2022
Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy.
Open access · greenAbstract read
In one paragraph
Article in Science (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
4.5field-weighted citation impact, top 4% of its field
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
27 citing papers in PubMed, 53 citations in OpenAlex.
- Structure-Guided Optimization of Novel Inhibitors ofJournal of medicinal chemistry · 2026Article
- Potent reaction hijacking inhibitors ofbioRxiv : the preprint server for biology · 2026Article
- Disruption of P. falciparum amino acid transporter elevates intracellular proline and induces resistance to Prolyl-tRNA synthetase inhibitors.Cell chemical biology · 2025Article
- Natural product-mediated reaction hijacking mechanism validates Plasmodium aspartyl-tRNA synthetase as an antimalarial drug target.PLoS pathogens · 2025Article
- Covalent inhibition ofiScience · 2025Article
- Towards next-generation treatment options to combat Plasmodium falciparum malaria.Nature reviews. Microbiology · 2025Review
- Revisiting theNPJ drug discovery · 2025Article
- A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo.PLoS pathogens · 2024Article
- A high content imaging assay for identification of specific inhibitors of nativeAntimicrobial agents and chemotherapy · 2024Article
- Transmission-Blocking Strategies for Malaria Eradication: Recent Advances in Small-Molecule Drug Development.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Specific glycine-dependent enzyme motion determines the potency of conformation selective inhibitors of threonyl-tRNA synthetase.Communications biology · 2024Article
- Structure-guided conversion from an anaplastic lymphoma kinase inhibitor into Plasmodium lysyl-tRNA synthetase selective inhibitors.Communications biology · 2024Article
- A high content imaging assay for identification of specific inhibitors of nativebioRxiv : the preprint server for biology · 2024Article
- Competitive Inhibition of Okanin againstInternational journal of molecular sciences · 2024Article
- Host metabolomic responses in recurrent P. vivax malaria.Scientific reports · 2024Article
- An OptimizedBio-protocol · 2024Article
- Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase.Nature communications · 2024Article
- Single-cell quantitative bioimaging ofmSphere · 2023Article
- Antimalarial drug discovery: progress and approaches.Nature reviews. Drug discovery · 2023Review
- A novel Modulator of Ring Stage Translation (MRST) gene alters artemisinin sensitivity inmSphere · 2023Article
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
37 authors at 9 institutions in 4 countries.
Stanley C Xie *Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0001-7003-4677
Riley D Metcalfe *Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0002-7154-780X
Elyse DunnDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0002-5941-2187
Craig J MortonDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0001-5452-5193
Shih-Chung HuangTakeda Development Center Americas, Inc., Cambridge, MA 02139, USA.ORCID 0000-0001-8510-4850
Tanya PuhalovichDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0001-5199-7267
Yawei DuDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0002-0829-1901
Sergio WittlinSwiss Tropical and Public Health Institute, 4051 Basel, Switzerland.
Shuai NieMelbourne Mass Spectrometry and Proteomics Facility, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0002-6425-972X
Madeline R LuthDepartment of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.ORCID 0000-0001-9059-1200
Liting MaTakeda Development Center Americas, Inc., Cambridge, MA 02139, USA.
Mi-Sook KimTakeda Development Center Americas, Inc., Cambridge, MA 02139, USA.
Charisse Flerida A PasajeDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0002-9780-3680
Krittikorn KumpornsinParasites and Microbes Programme, Wellcome Sanger Institute, Hinxton CB10 1SA, UK.ORCID 0000-0001-9427-7139
Carlo GiannangeloDrug Delivery, Disposition, and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.ORCID 0000-0002-6654-7266
Fiona J HoughtonDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0002-4420-2953
Alisje ChurchyardDepartment of Life Sciences, Imperial College London, London SW7 2AZ, UK.ORCID 0000-0002-4726-6397
Mufuliat T FamodimuDepartment of Life Sciences, Imperial College London, London SW7 2AZ, UK.ORCID 0000-0002-8852-1040
Daniel C BarryDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0001-5288-8863
David L GillettDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0002-1239-6888
Sumanta DeyDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0002-5945-976X
Clara C KosasihDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0003-3249-7341
William NewmanDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0003-1323-3068
Jacquin C NilesDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0002-6250-8796
Marcus C S LeeParasites and Microbes Programme, Wellcome Sanger Institute, Hinxton CB10 1SA, UK.ORCID 0000-0002-4973-0915
Jake BaumDepartment of Life Sciences, Imperial College London, London SW7 2AZ, UK.ORCID 0000-0002-0275-352X
Sabine OttilieDepartment of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Elizabeth A WinzelerDepartment of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-4049-2113
Darren J CreekDrug Delivery, Disposition, and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.ORCID 0000-0001-7497-7082
Nicholas WilliamsonMelbourne Mass Spectrometry and Proteomics Facility, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0002-2173-3452
Michael W ParkerDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0002-3101-1138
Stephen BrandMedicines for Malaria Venture, P.O. Box 1826, 20, Route de Pré-Bois, 1215 Geneva 15, Switzerland.ORCID 0000-0002-7010-5348
Steven P Langston *Takeda Development Center Americas, Inc., Cambridge, MA 02139, USA.ORCID 0000-0001-5840-0005
Lawrence R Dick *Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0002-6880-0405
Michael D W Griffin *Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0001-9845-7735
Alexandra E Gould *Takeda Development Center Americas, Inc., Cambridge, MA 02139, USA.ORCID 0000-0002-1657-5891
Leann Tilley *Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0001-9910-0199
The University of Melbourne · AUTakeda (United States) · USImperial College London · GBMassachusetts Institute of Technology · USUniversity of California San Diego · USMonash University · AUWellcome Sanger Institute · GBMedicines for Malaria Venture · CHSwiss Tropical and Public Health Institute · CH
Funding
Training Program in Basic Clinical GeneticsT32GM008666 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMILTON, BRUCE A · 1998 to 2021
$8.6MDiscovery of long-acting, chemoprotective antimalarial compoundsR01AI152533 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WINZELER, ELIZABETH A · 2020 to 2024
$3.5MNIAID NIH HHS R01 AI152533NIGMS NIH HHS T32 GM008666Wellcome Trust 100993Wellcome Trust 206194
Abstract
Aminoacyl transfer RNA (tRNA) synthetases (aaRSs) are attractive drug targets, and we present class I and II aaRSs as previously unrecognized targets for adenosine 5'-monophosphate-mimicking nucleoside sulfamates. The target enzyme catalyzes the formation of an inhibitory amino acid-sulfamate conjugate through a reaction-hijacking mechanism. We identified adenosine 5'-sulfamate as a broad-specificity compound that hijacks a range of aaRSs and ML901 as a specific reagent a specific reagent that hijacks a single aaRS in the malaria parasite
Indexed as
AntimalarialsMalaria, FalciparumMolecular Targeted TherapyPlasmodium falciparumProtein BiosynthesisProtozoan ProteinsTyrosine-tRNA LigaseAdenosineAnimalsCrystallography, X-RayHumansMiceProtein ConformationSulfonic AcidsAdenosineAntimalarialsProtozoan Proteinssulfamic acidSulfonic AcidsTyrosine-tRNA Ligase
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
Read underepoch 390
Registered trials
None linked
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.