Evidence map›Paper›PMID 17594497›Full record

ArticleBMC structural biology2007

X-ray structures of Na-GST-1 and Na-GST-2 two glutathione S-transferase from the human hookworm Necator americanus.

Oluwatoyin A Asojo, Kohei Homma, Meghan Sedlacek, Michelle Ngamelue, Gaddam N Goud, Bin Zhan, Vehid Deumic, Oluyomi Asojo, Peter J Hotez

Open access · bronzeAbstract read
In one paragraph

Article in BMC structural biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

24 citing papers in PubMed, 47 citations in OpenAlex.

  1. Trial
  2. Article
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  5. The yin and yang of human soil-transmitted helminth infections.International journal for parasitology · 2021
    Review
  6. Review
  7. Article
  8. GlutathioneDrug design, development and therapy · 2018
    Review
  9. Article
  10. Article
  11. Article
  12. Article
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  14. Article
  15. Structure of monomeric Na-GST-3, a glutathione S-transferase from the major human hookworm parasite Necator americanus.Acta crystallographica. Section F, Structural biology and crystallization communications · 2013
    Article
  16. Article
  17. Article
  18. Review
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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

9 authors at 3 institutions in 1 country.

Oluwatoyin A AsojoDepartment of Pathology and Microbiology, College of Medicine Nebraska Medical Center, Omaha, NE 68198-6495, USA. oasojo@unmc.edu
Kohei Homma
Meghan Sedlacek
Michelle Ngamelue
Gaddam N Goud
Bin Zhan
Vehid Deumic
Oluyomi Asojo
Peter J Hotez
Nebraska Medical Center · USGeorge Washington University · USWashington University Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHuman hookworm infection is a major cause of anemia and malnutrition of adults and children in the developing world. As part of on-going efforts to control hookworm infection, The Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective L3 larval stages and adult stages of the parasite. Adult stage antigens include the cytosolic glutathione-S-transferases (GSTs). Nematode GSTs facilitate the inactivation and degradation of a variety of electrophilic substrates (drugs) via the nucleophilic addition of reduced glutathione. Parasite GSTs also play significant roles in multi-drug resistance and the modulation of host-immune defense mechanisms.

resultsThe crystal structures of Na-GST-1 and Na-GST-2, two major GSTs from Necator americanus the main human hookworm parasite, have been solved at the resolution limits of 2.4 A and 1.9 A respectively. The structure of Na-GST-1 was refined to R-factor 18.9% (R-free 28.3%) while that of Na-GST-2 was refined to R-factor 17.1% (R-free 21.7%). Glutathione usurped during the fermentation process in bound in the glutathione binding site (G-site) of each monomer of Na-GST-2. Na-GST-1 is uncomplexed and its G-site is abrogated by Gln 50. These first structures of human hookworm parasite GSTs could aid the design of novel hookworm drugs.

conclusionThe 3-dimensional structures of Na-GST-1 and Na-GST-2 show two views of human hookworm GSTs. While the GST-complex structure of Na-GST-2 reveals a typical GST G-site that of Na-GST-1 suggests that there is some conformational flexibility required in order to bind the substrate GST. In addition, the overall binding cavities for both are larger, more open, as well as more accessible to diverse ligands than those of GSTs from organisms that have other major detoxifying mechanisms. The results from this study could aid in the design of novel drugs and vaccine antigens.

Indexed as

Amino Acid SequenceAncylostomatoideaAnimalsCrystallography, X-RayDimerizationDrug DesignGlutathione TransferaseHumansModels, MolecularMolecular Sequence DataProtease InhibitorsProtein Structure, QuaternaryProtein Structure, TertiarySequence AlignmentSequence Homology, Amino AcidStructural Homology, ProteinGlutathione TransferaseProtease Inhibitors

Identifiers

PMID17594497
PMCPMC1924862
OpenAlexW2113014090

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LicenceCC BY
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Registered trials

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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.