ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
HIV proteinase inhibitors target the Ddi1-like protein of Leishmania parasites.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 43 citations in OpenAlex.
- Domains in Action: Understanding Ddi1's Diverse Functions in the Ubiquitin-Proteasome System.International journal of molecular sciences · 2024Review
- Structural and functional insights into the DNA damage-inducible protein 1 (Ddi1) from protozoa.Current research in structural biology · 2022Article
- Lopinavir and Nelfinavir Induce the Accumulation of Crystalloid Lipid Inclusions within the Reservosomes ofTropical medicine and infectious disease · 2021Article
- Nanodiagnostics in leishmaniasis: A new frontiers for early elimination.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2021Review
- Article
- Nelfinavir Inhibits the TCF11/Nrf1-Mediated Proteasome Recovery Pathway in Multiple Myeloma.Cancers · 2020Article
- Dimer Interface Organization is a Main Determinant of Intermonomeric Interactions and Correlates with Evolutionary Relationships of Retroviral and Retroviral-Like Ddi1 and Ddi2 Proteases.International journal of molecular sciences · 2020Article
- Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism of Leishmania amazonensis promastigotes.Parasitology · 2018Article
- Crystal structure of the retroviral protease-like domain of a protozoal DNA damage-inducible 1 protein.FEBS open bio · 2018Article
- Article
- Antileishmanial activity of antiretroviral drugs combined with miltefosine.Parasitology research · 2016Article
- Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family.Scientific reports · 2016Article
- Human DNA-Damage-Inducible 2 Protein Is Structurally and Functionally Distinct from Its Yeast Ortholog.Scientific reports · 2016Article
- Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis.Chemical reviews · 2014Review
- Ddi1-like protein from Leishmania major is an active aspartyl proteinase.Cell stress & chaperones · 2013Article
- Nelfinavir is effective in inhibiting the multiplication and aspartic peptidase activity of Leishmania species, including strains obtained from HIV-positive patients.The Journal of antimicrobial chemotherapy · 2013Article
- Aspartic peptidases of human pathogenic trypanosomatids: perspectives and trends for chemotherapy.Current medicinal chemistry · 2013Review
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 2 countries.
Funding
Abstract
HIV proteinase inhibitors reduce the levels of Leishmania parasites in vivo and in vitro, but their biochemical target is unknown. We have identified an ortholog of the yeast Ddi1 protein as the only member of the aspartic proteinase family in Leishmania parasites, and in this study we investigate this protein as a potential target for the drugs. To date, no enzyme assay has been developed for the Ddi1 proteins, but Saccharomyces cerevisiae lacking the DDI1 gene secrete high levels of protein into the medium. We developed an assay in which these knockout yeast were functionally complemented to low secretion by introduction of genes encoding Ddi1 orthologs from Leishmania major or humans. Plasmid alone controls gave no complementation. Treatment of the Ddi1 transformants with HIV proteinase inhibitors showed differential effects dependent on the origin of the Ddi1. Dose responses allowed calculation of IC(50) values; e.g., for nelfinavir, of 3.4 μM (human Ddi1) and 0.44 μM (Leishmania Ddi1). IC(50) values with Leishmania constructs mirror the potency of inhibitors against parasites. Our results show that Ddi1 proteins are targets of HIV proteinase inhibitors and indicates the Leishmania Ddi1 as the likely target for these drugs and a potential target for antiparasitic therapy.
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.