Evidence map›Paper›PMID 31757046›Full record

ArticleMarine drugs2019

Probing the Interactions of Sulfur-Containing Histidine Compounds with Human Gamma-Glutamyl Transpeptidase.

Alfonsina Milito, Mariarita Brancaccio, Michael Lisurek, Mariorosario Masullo, Anna Palumbo, Immacolata Castellano

Open access · goldAbstract read
In one paragraph

Article in Marine drugs, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.5field-weighted citation impact, top 21% 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

13 citing papers in PubMed, 18 citations in OpenAlex.

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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

6 authors at 3 institutions in 2 countries.

Alfonsina MilitoDept. of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, 80121 Naples, Italy.
Mariarita BrancaccioDept. of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, 80121 Naples, Italy.
Michael LisurekDept. of Computational Chemistry and Drug Design, Leibniz-Forschungsinstitut für Molekulare Pharmakologie, 13125 Berlin, Germany.
Mariorosario MasulloDept. of Human Movement Sciences and Wellbeing, University of Naples "Parthenope", 80133 Naples, Italy.
Anna PalumboDept. of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, 80121 Naples, Italy.
Immacolata CastellanoDept. of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, 80121 Naples, Italy.
Stazione Zoologica Anton Dohrn · ITLeibniz-Forschungsinstitut für Molekulare Pharmakologie · DEParthenope University of Naples · IT

Funding

Horizon 2020 No 654008
6 · The paper itself

Abstract

Gamma-glutamyl transpeptidase (GGT) is a cell surface enzyme involved in glutathione metabolism and maintenance of redox homeostasis. High expression of GGT on tumor cells is associated with an increase of cell proliferation and resistance against chemotherapy. GGT inhibitors that have been evaluated in clinical trials are too toxic for human use. We have previously identified ovothiols, 5(Nπ)-methyl-thiohistidines of marine origin, as non-competitive-like inhibitors of GGT that are more potent than the known GGT inhibitor, 6-diazo-5-oxo-l-norleucine (DON), and are not toxic for human embryonic cells. We extended these studies to the desmethylated form of ovothiol, 5-thiohistidine, and confirmed that this ovothiol derivative also acts as a non-competitive-like GGT inhibitor, with a potency comparable to ovothiol. We also found that both 5-thiohistidine derivatives act as reversible GGT inhibitors compared to the irreversible DON. Finally, we probed the interactions of 5-thiohistidines with GGT by docking analysis and compared them with the 2-thiohistidine ergothioneine, the physiological substrate glutathione, and the DON inhibitor. Overall, our results provide new insight for further development of 5-thiohistidine derivatives as therapeutics for GGT-positive tumors.

Indexed as

Aquatic OrganismsAzo CompoundsCell ProliferationDrug DevelopmentDrug Resistance, NeoplasmEnzyme Assaysgamma-GlutamyltransferaseGlutathioneHEK293 CellsHistidineHumansMolecular Docking SimulationNeoplasmsNorleucineSubstrate SpecificitySulfur Compounds6-diazo-5-oxonorleucineAzo Compoundsgamma-GlutamyltransferaseGlutathioneHistidineNorleucineSulfur Compoundsdocking simulationenzymatic inhibitionergothioneineGGTmarine antioxidantmarine drugsmolecular interactionsovothiolsulfur-containing histidineγ-glutamyl transpeptidase

Identifiers

PMID31757046
PMCPMC6949936
OpenAlexW2991376540

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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.