Evidence map›Paper›PMID 30532032›Full record

ArticleNature communications2018

Inhibitor binding mode and allosteric regulation of Na

Paola Bisignano, Chiara Ghezzi, Hyunil Jo, Nicholas F Polizzi, Thorsten Althoff, Chakrapani Kalyanaraman, Rosmarie Friemann, Matthew P Jacobson, Ernest M Wright, Michael Grabe

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

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

37 citing papers in PubMed, 51 citations in OpenAlex.

  1. Dapagliflozin Beyond Glucose Lowering: Mechanisms of Renal and Systemic Protection.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Review
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  10. Review
  11. Review
  12. Article
  13. Article
  14. Use of Animal Models for Investigating Cardioprotective Roles of SGLT2 Inhibitors.Journal of cardiovascular translational research · 2023
    Review
  15. Article
  16. Collective Domain Motion Facilitates Water Transport in SGLT1.International journal of molecular sciences · 2023
    Article
  17. Article
  18. Article
  19. Review
  20. Structural mechanism of SGLT1 inhibitors.Nature communications · 2022
    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 3 institutions in 2 countries.

Paola BisignanoDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0003-1789-762X
Chiara GhezziDepartment of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1751, USA.
Hyunil JoDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-4863-0779
Nicholas F PolizziDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA, 94158, USA.
Thorsten AlthoffDepartment of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1751, USA.
Chakrapani KalyanaramanDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA, 94158, USA.
Rosmarie FriemannDepartment of Chemistry and Molecular Biology, Centre for Antibiotic Resistance (CARe) at University of Gothenburg, SE-40530, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-5633-2894
Matthew P JacobsonDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0001-6262-655X
Ernest M WrightDepartment of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1751, USA. EWright@mednet.ucla.edu.ORCID http://orcid.org/0000-0002-1023-4391
Michael GrabeDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA, 94158, USA. michael.grabe@ucsf.edu.
University of California, San Francisco · USUniversity of California, Los Angeles · USUniversity of Gothenburg · SE

Funding

Computational Studies of Sodium SymportersR01GM089740 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GRABE, MICHAEL · 2011 to 2020
$2.8M
NIGMS NIH HHS R01 GM089740
6 · The paper itself

Abstract

Sodium-dependent glucose transporters (SGLTs) exploit sodium gradients to transport sugars across the plasma membrane. Due to their role in renal sugar reabsorption, SGLTs are targets for the treatment of type 2 diabetes. Current therapeutics are phlorizin derivatives that contain a sugar moiety bound to an aromatic aglycon tail. Here, we develop structural models of human SGLT1/2 in complex with inhibitors by combining computational and functional studies. Inhibitors bind with the sugar moiety in the sugar pocket and the aglycon tail in the extracellular vestibule. The binding poses corroborate mutagenesis studies and suggest a partial closure of the outer gate upon binding. The models also reveal a putative Na

Indexed as

Allosteric RegulationAnimalsBinding SitesFemaleGlucoseHumansOocytesPhlorhizinProtein BindingSodiumSodium-Glucose Transporter 1Sodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsSymportersXenopus laevisGlucosePhlorhizinSodiumSodium-Glucose Transporter 1Sodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsSymporters

Identifiers

PMID30532032
PMCPMC6286348
OpenAlexW2902642226

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.