ArticleProceedings of the National Academy of Sciences of the United States of America2012
Leishmania TDR1 structure, a unique trimeric glutathione transferase capable of deglutathionylation and antimonial prodrug activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Leishmania spp. genetic factors associated with cutaneous leishmaniasis antimony pentavalent drug resistance: a systematic review.Memorias do Instituto Oswaldo Cruz · 2024Pooled it
- Computational and experimental studies to discover a promising lead compound, chemically related to natural acetylene acetogenins from Porcelia macrocarpa, against amastigotes of Leishmania (L.) infantum.Journal of computer-aided molecular design · 2025Article
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
- Insights from Leishmania (Viannia) guyanensis in vitro behavior and intercellular communication.Parasites & vectors · 2021Article
- Hypothalamic and ovarian transcriptome profiling reveals potential candidate genes in low and high egg production of white Muscovy ducks (Cairina moschata).Poultry science · 2021Article
- Cytotoxicity of Essential OilMolecules (Basel, Switzerland) · 2021Article
- Kinetic studies reveal a key role of a redox-active glutaredoxin in the evolution of the thiol-redox metabolism of trypanosomatid parasites.The Journal of biological chemistry · 2019Article
- Molecular Basis of the Leishmanicidal Activity of the Antidepressant Sertraline as a Drug Repurposing Candidate.Antimicrobial agents and chemotherapy · 2018Article
- Interaction of ascaridole, carvacrol, and caryophyllene oxide from essential oil of Chenopodium ambrosioides L. with mitochondria in Leishmania and other eukaryotes.Phytotherapy research : PTR · 2018Article
- Quantitative proteome and phosphoproteome analyses highlight the adherent population during Trypanosoma cruzi metacyclogenesis.Scientific reports · 2017Article
- The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations.Molecules (Basel, Switzerland) · 2016Review
- Drug resistance in eukaryotic microorganisms.Nature microbiology · 2016Review
- Systems approach to metal-based pharmacology.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- An alternate pathway of arsenate resistance in E. coli mediated by the glutathione S-transferase GstB.ACS chemical biology · 2015Article
- A Multiplatform Metabolomic Approach to the Basis of Antimonial Action and Resistance in Leishmania infantum.PloS one · 2015Article
- The still mysterious roles of cysteine-containing glutathione transferases in plants.Frontiers in pharmacology · 2014Review
- In-silico Leishmania target selectivity of antiparasitic terpenoids.Molecules (Basel, Switzerland) · 2013Article
- Prodrug activation: glutaredoxin family tree.Nature chemical biology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Thiol-dependent reductase I (TDR1), an enzyme found in parasitic Leishmania species and Trypanosoma cruzi, is implicated in deglutathionylation and activation of antimonial prodrugs used to treat leishmaniasis. The 2.3 Å resolution structure of TDR1 reveals a unique trimer of subunits each containing two glutathione-S-transferase (GST) domains. The similarities of individual domains and comparisons with GST classes suggest that TDR1 evolved by gene duplication, diversification, and gene fusion; a combination of events previously unknown in the GST protein superfamily and potentially explaining the distinctive enzyme properties of TDR1. The deglutathionylation activity of TDR1 implies that glutathione itself has regulatory intracellular roles in addition to being a precursor for trypanothione, the major low mass thiol present in trypanosomatids. We propose that activation of antiparasite Sb(V)-drugs is a legacy of the deglutathionylation activity of TDR1 and involves processing glutathione adducts with concomitant reduction of the metalloid to active Sb(III) species.
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.