Evidence map›Paper›PMID 29518650›Full record

ArticleInternational journal for parasitology. Drugs and drug resistance2018

Characterization and validation of Entamoeba histolytica pantothenate kinase as a novel anti-amebic drug target.

Arif Nurkanto, Ghulam Jeelani, Takehiro Yamamoto, Yoshiko Naito, Takako Hishiki, Mihoko Mori, Makoto Suematsu, Kazuro Shiomi, Tetsuo Hashimoto, Tomoyoshi Nozaki

Open access · goldAbstract read
In one paragraph

Article in International journal for parasitology. Drugs and drug resistance, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.0field-weighted citation impact, top 24% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Microbiology spectrum · 2025
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  7. Characterization ofFrontiers in cellular and infection microbiology · 2021
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  8. Revisiting Drug Development Against the Neglected Tropical Disease, Amebiasis.Frontiers in cellular and infection microbiology · 2020
    Review
  9. Lipids inFrontiers in cellular and infection microbiology · 2020
    Review
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 2 countries.

Arif NurkantoGraduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan; Department of Parasitology, National Institute of Infectious Diseases (NIID), Tokyo, Japan; Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Japan; Research Center for Biology, Indonesia Institute of Sciences (LIPI), Cibinong, Indonesia.
Ghulam JeelaniDepartment of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Japan.
Takehiro YamamotoDepartment of Biochemistry, School of Medicine, Keio University, Tokyo, Japan.
Yoshiko NaitoClinical and Translational Research Center, Keio University School of Medicine, Japan.
Takako HishikiDepartment of Biochemistry, School of Medicine, Keio University, Tokyo, Japan; Clinical and Translational Research Center, Keio University School of Medicine, Japan.
Mihoko MoriKitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
Makoto SuematsuDepartment of Biochemistry, School of Medicine, Keio University, Tokyo, Japan.
Kazuro ShiomiKitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
Tetsuo HashimotoGraduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.
Tomoyoshi NozakiDepartment of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Japan. Electronic address: nozaki@m.u-tokyo.ac.jp.
Keio University · JPKitasato Institute Hospital · JPUniversity of Tsukuba · JPThe University of Tokyo · JPTokyo University of Science · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Coenzyme A (CoA), as a cofactor involved in >100 metabolic reactions, is essential to the basic biochemistry of life. Here, we investigated the CoA biosynthetic pathway of Entamoeba histolytica (E. histolytica), an enteric protozoan parasite responsible for human amebiasis. We identified four key enzymes involved in the CoA pathway: pantothenate kinase (PanK, EC 2.7.1.33), bifunctional phosphopantothenate-cysteine ligase/decarboxylase (PPCS-PPCDC), phosphopantetheine adenylyltransferase (PPAT) and dephospho-CoA kinase (DPCK). Cytosolic enzyme PanK, was selected for further biochemical, genetic, and phylogenetic characterization. Since E. histolytica PanK (EhPanK) is physiologically important and sufficiently divergent from its human orthologs, this enzyme represents an attractive target for the development of novel anti-amebic chemotherapies. Epigenetic gene silencing of PanK resulted in a significant reduction of PanK activity, intracellular CoA concentrations, and growth retardation in vitro, reinforcing the importance of this gene in E. histolytica. Furthermore, we screened the Kitasato Natural Products Library for inhibitors of recombinant EhPanK, and identified 14 such compounds. One compound demonstrated moderate inhibition of PanK activity and cell growth at a low concentration, as well as differential toxicity towards E. histolytica and human cells.

Indexed as

AmebiasisAntiprotozoal AgentsBiological ProductsBiosynthetic PathwaysCoenzyme ADrug Delivery SystemsDrug DiscoveryEntamoeba histolyticaEpigenomicsGene SilencingHumansNucleotidyltransferasesPeptide SynthasesPhosphotransferases (Alcohol Group Acceptor)PhylogenySmall Molecule LibrariesAntiprotozoal AgentsBiological ProductsCoenzyme ANucleotidyltransferasespantetheine-phosphate adenylyltransferasepantothenate kinasePeptide Synthasesphosphopantothenoyl-cysteine synthetasePhosphotransferases (Alcohol Group Acceptor)Small Molecule LibrariesAmebiasisCoenzyme ADrug developmentEntamoeba histolyticaGene silencingPantothenate kinase

Identifiers

PMID29518650
PMCPMC6114107
OpenAlexW2794042310

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.