Evidence map›Paper›PMID 34887566›Full record

ArticleNature structural & molecular biology2021

Fungicidal amphotericin B sponges are assemblies of staggered asymmetric homodimers encasing large void volumes.

Agnieszka Lewandowska, Corinne P Soutar, Alexander I Greenwood, Evgeny Nimerovsky, Ashley M De Lio, Jordan T Holler, Grant S Hisao, Anuj Khandelwal, Jiabao Zhang, Anna M SantaMaria and 4 more

Registry-linked trialAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07215273 (A Phase 2, Multicenter, Randomized, Double-blind Study of Safety and Efficacy of EL219), which is not on this map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
–field-weighted citation impact
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.

NCT07215273 phase2recruitingnot on this mapstarted 2026, after this paper: background citation

A Phase 2, Multicenter, Randomized, Double-blind Study of Safety and Efficacy of EL219 (Turletricin) Versus Liposomal Amphotericin B or Voriconazole for Early Antifungal Therapy of Invasive Mould Infections (TREAT-1)

TypeinterventionalSponsorElion Therapeutics, Inc.Ran2026 to 2026Enrolled60ConditionsInvasive Mould InfectionArmsEL219, Active Comparator- IV Antifungal (LAmB or voriconazole)
3 · Its place in the literature

Who cites it

27 citing papers in PubMed.

  1. Article
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  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. OPTO: Automated Optimization for Solid-State NMR Spectroscopy.Journal of the American Chemical Society · 2025
    Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. A complete 3D-printed tool kit for Solid-State NMR sample and rotor handling.Journal of magnetic resonance (San Diego, Calif. : 1997) · 2024
    Article
  20. Solid-State NMRJournal of magnetic resonance (San Diego, Calif. : 1997) · 2024
    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

14 authors.

Agnieszka LewandowskaDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.ORCID http://orcid.org/0000-0001-8593-0781
Corinne P SoutarDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.ORCID http://orcid.org/0000-0002-2087-7622
Alexander I GreenwoodDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Evgeny NimerovskyDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Ashley M De LioDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Jordan T HollerDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Grant S HisaoDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.ORCID http://orcid.org/0000-0003-4631-9722
Anuj KhandelwalDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Jiabao ZhangDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Anna M SantaMariaDepartment of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Charles D SchwietersComputational Biomolecular Magnetic Resonance Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-4216-4658
Taras V PogorelovDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA. pogorelo@illinois.edu.ORCID http://orcid.org/0000-0001-5851-7721
Martin D BurkeDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA. mdburke@illinois.edu.ORCID http://orcid.org/0000-0001-7963-7140
Chad M RienstraDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA. crienstra@wisc.edu.ORCID http://orcid.org/0000-0002-9912-5596

Funding

Molecular Prosthetics and Lego ChemistryR35GM118185 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI Martin D Burke · 2016 to 2026
$6.6M
Technologies for Solid-State NMR Data CollectionP41GM136463 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI HENZLER-WILDMAN, KATHERINE ANNE, RIENSTRA, CHAD M · 2021 to 2025
$6.4M
Toolkit for High-Resolution Structure and Dynamics of Functional LipidsR01GM123455 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI MORRISSEY, JAMES H., RIENSTRA, CHAD M · 2016 to 2020
$5.0M
Structures of Amphotericin-Sterol ComplexesR01GM112845 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI RIENSTRA, CHAD M · 2015 to 2018
$1.8M
NIGMS NIH HHS P41 GM136463NIGMS NIH HHS R01 GM112845NIGMS NIH HHS R01 GM123455NIGMS NIH HHS R35 GM118185
6 · The paper itself

Abstract

Amphotericin B (AmB) is a powerful but toxic fungicide that operates via enigmatic small molecule-small molecule interactions. This mechanism has challenged the frontiers of structural biology for half a century. We recently showed AmB primarily forms extramembranous aggregates that kill yeast by extracting ergosterol from membranes. Here, we report key structural features of these antifungal 'sponges' illuminated by high-resolution magic-angle spinning solid-state NMR, in concert with simulated annealing and molecular dynamics computations. The minimal unit of assembly is an asymmetric head-to-tail homodimer: one molecule adopts an all-trans C1-C13 motif, the other a C6-C7-gauche conformation. These homodimers are staggered in a clathrate-like lattice with large void volumes similar to the size of sterols. These results illuminate the atomistic interactions that underlie fungicidal assemblies of AmB and suggest this natural product may form biologically active clathrates that host sterol guests.

Indexed as

Amphotericin BAntifungal AgentsCell MembraneCells, CulturedErgosterolHumansImmunocompromised HostInvasive Fungal InfectionsMolecular ConformationMolecular Dynamics SimulationNuclear Magnetic Resonance, BiomolecularStreptomycesAmphotericin BAntifungal AgentsErgosterol

Identifiers

PMID34887566
PMCPMC9336184

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Registered trials

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.