Evidence map›Paper›PMID 31621581›Full record

ArticleeLife2019

Identification of an allosteric binding site on the human glycine transporter, GlyT2, for bioactive lipid analgesics.

Shannon N Mostyn, Katie A Wilson, Alexandra Schumann-Gillett, Zachary J Frangos, Susan Shimmon, Tristan Rawling, Renae M Ryan, Megan L O'Mara, Robert J Vandenberg

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

26 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Mechanisms of transport and analgesic compounds recognition by glycine transporter 2.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Future opportunities in solute carrier structural biology.Nature structural & molecular biology · 2024
    Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Engineering an Allosteric Control of Protein Function.The journal of physical chemistry. B · 2021
    Review
  18. Article
  19. Glycine Transporter 2: Mechanism and Allosteric Modulation.Frontiers in molecular biosciences · 2021
    Review
  20. Heteromeric Solute Carriers: Function, Structure, Pathology and Pharmacology.Advances in experimental medicine and biology · 2021
    Review
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.

Shannon N MostynSchool of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
Katie A WilsonResearch School of Chemistry, College of Science, The Australian National University, Canberra, Australia.
Alexandra Schumann-GillettResearch School of Chemistry, College of Science, The Australian National University, Canberra, Australia.
Zachary J FrangosSchool of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
Susan ShimmonSchool of Mathematical and Physical Sciences, University of Technology Sydney, Sydney, Australia.
Tristan RawlingSchool of Mathematical and Physical Sciences, University of Technology Sydney, Sydney, Australia.
Renae M RyanSchool of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
Megan L O'MaraResearch School of Chemistry, College of Science, The Australian National University, Canberra, Australia.
Robert J VandenbergSchool of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.ORCID 0000-0003-1523-4814
The University of Sydney · AUAustralian National University · AUUniversity of Technology Sydney · AU

Funding

Department of Education, Employment and Workplace Relations, Australian Government Australian Postgraduate AwardDepartment of Education, Employment and Workplace Relations, Australian Government Research Training AwardNational Health and Medical Research Council APP1144429Westpac Bicentennial Foundation Westpac Scholars Trust Future Leaders Scholarship
6 · The paper itself

Abstract

The treatment of chronic pain is poorly managed by current analgesics, and there is a need for new classes of drugs. We recently developed a series of bioactive lipids that inhibit the human glycine transporter GlyT2 (SLC6A5) and provide analgesia in animal models of pain. Here, we have used functional analysis of mutant transporters combined with molecular dynamics simulations of lipid-transporter interactions to understand how these bioactive lipids interact with GlyT2. This study identifies a novel extracellular allosteric modulator site formed by a crevice between transmembrane domains 5, 7, and 8, and extracellular loop 4 of GlyT2. Knowledge of this site could be exploited further in the development of drugs to treat pain, and to identify other allosteric modulators of the SLC6 family of transporters.

Indexed as

Lipid MetabolismAnalgesicsBinding SitesGlycine Plasma Membrane Transport ProteinsHumansMolecular Dynamics SimulationProtein BindingProtein ConformationAnalgesicsGlycine Plasma Membrane Transport ProteinsSLC6A5 protein, humanallosteric inhibitoranalgesicbioactive lipidbiochemistrychemical biologyglycine transporterhumanlipid binding site

Identifiers

PMID31621581
PMCPMC6797481
OpenAlexW2980859185

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.