Fungicidal amphotericin B sponges are assemblies of staggered asymmetric homodimers encasing large void volumes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-12-09

AUTHORS

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, Charles D. Schwieters, Taras V. Pogorelov, Martin D. Burke, Chad M. Rienstra

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. More... »

PAGES

972-981

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41594-021-00685-4

DOI

http://dx.doi.org/10.1038/s41594-021-00685-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1143745027

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/34887566


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biochemistry and Cell Biology", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Amphotericin B", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antifungal Agents", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Membrane", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cells, Cultured", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Ergosterol", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Immunocompromised Host", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Invasive Fungal Infections", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Molecular Conformation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Molecular Dynamics Simulation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Nuclear Magnetic Resonance, Biomolecular", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Streptomyces", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA", 
          "id": "http://www.grid.ac/institutes/grid.14003.36", 
          "name": [
            "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
            "Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lewandowska", 
        "givenName": "Agnieszka", 
        "id": "sg:person.013761063555.16", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013761063555.16"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA", 
          "id": "http://www.grid.ac/institutes/grid.14003.36", 
          "name": [
            "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
            "Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Soutar", 
        "givenName": "Corinne P.", 
        "id": "sg:person.012547100167.71", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012547100167.71"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
          "id": "http://www.grid.ac/institutes/grid.35403.31", 
          "name": [
            "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Greenwood", 
        "givenName": "Alexander I.", 
        "id": "sg:person.014251054157.38", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014251054157.38"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
          "id": "http://www.grid.ac/institutes/grid.35403.31", 
          "name": [
            "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Nimerovsky", 
        "givenName": "Evgeny", 
        "id": "sg:person.01372371261.09", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01372371261.09"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Computation-based Science and Technology Research Center, The Cyprus Institute, Aglantzia, Cyprus", 
          "id": "http://www.grid.ac/institutes/grid.426429.f", 
          "name": [
            "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
            "National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
            "Computation-based Science and Technology Research Center, The Cyprus Institute, Aglantzia, Cyprus"
          ], 
          "type": "Organization"
        }, 
        "familyName": "De Lio", 
        "givenName": "Ashley M.", 
        "id": "sg:person.0600437154.42", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0600437154.42"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
          "id": "http://www.grid.ac/institutes/grid.35403.31", 
          "name": [
            "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Holler", 
        "givenName": "Jordan T.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
          "id": "http://www.grid.ac/institutes/grid.35403.31", 
          "name": [
            "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Hisao", 
        "givenName": "Grant S.", 
        "id": "sg:person.01362440503.25", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01362440503.25"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
          "id": "http://www.grid.ac/institutes/grid.35403.31", 
          "name": [
            "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Khandelwal", 
        "givenName": "Anuj", 
        "id": "sg:person.013253331401.54", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013253331401.54"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
          "id": "http://www.grid.ac/institutes/grid.35403.31", 
          "name": [
            "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Zhang", 
        "givenName": "Jiabao", 
        "id": "sg:person.013627312231.29", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013627312231.29"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
          "id": "http://www.grid.ac/institutes/grid.35403.31", 
          "name": [
            "Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "SantaMaria", 
        "givenName": "Anna M.", 
        "id": "sg:person.011205457727.06", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011205457727.06"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Computational Biomolecular Magnetic Resonance Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA", 
          "id": "http://www.grid.ac/institutes/grid.419635.c", 
          "name": [
            "Computational Biomolecular Magnetic Resonance Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Schwieters", 
        "givenName": "Charles D.", 
        "id": "sg:person.01315704334.08", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01315704334.08"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
          "id": "http://www.grid.ac/institutes/grid.35403.31", 
          "name": [
            "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
            "National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
            "School of Chemical Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
            "Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
            "Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Pogorelov", 
        "givenName": "Taras V.", 
        "id": "sg:person.01046437345.66", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01046437345.66"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Carle-Illinois College of Medicine, University of Illinois at Urbana-Champaign, Champaign, IL, USA", 
          "id": "http://www.grid.ac/institutes/grid.35403.31", 
          "name": [
            "Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
            "Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
            "Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA", 
            "Carle-Illinois College of Medicine, University of Illinois at Urbana-Champaign, Champaign, IL, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Burke", 
        "givenName": "Martin D.", 
        "id": "sg:person.0704253111.66", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0704253111.66"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI, USA", 
          "id": "http://www.grid.ac/institutes/grid.509573.d", 
          "name": [
            "Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA", 
            "National Magnetic Resonance Facility at Madison, University of Wisconsin-Madison, Madison, WI, USA", 
            "Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Rienstra", 
        "givenName": "Chad M.", 
        "id": "sg:person.01260316751.40", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01260316751.40"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1007/bf00533485", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015541359", 
          "https://doi.org/10.1007/bf00533485"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/s41586-019-1018-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1112734622", 
          "https://doi.org/10.1038/s41586-019-1018-5"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrm.2017.16", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1084129732", 
          "https://doi.org/10.1038/nrm.2017.16"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nchembio.663", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046204097", 
          "https://doi.org/10.1038/nchembio.663"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1758-2946-4-17", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012254507", 
          "https://doi.org/10.1186/1758-2946-4-17"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nsmb.3194", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016142352", 
          "https://doi.org/10.1038/nsmb.3194"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10858-009-9333-z", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037424361", 
          "https://doi.org/10.1007/s10858-009-9333-z"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/262698a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045561900", 
          "https://doi.org/10.1038/262698a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrd.2017.46", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085393524", 
          "https://doi.org/10.1038/nrd.2017.46"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nchembio.1496", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049690615", 
          "https://doi.org/10.1038/nchembio.1496"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2021-12-09", 
    "datePublishedReg": "2021-12-09", 
    "description": "Amphotericin B (AmB) is a powerful but toxic fungicide that operates via enigmatic small molecule\u2013small 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 \u2018sponges\u2019 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\u2013C13 motif, the other a C6\u2013C7-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.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/s41594-021-00685-4", 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.9534797", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.6375863", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.3859076", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.5244336", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1295033", 
        "issn": [
          "1545-9993", 
          "2331-365X"
        ], 
        "name": "Nature Structural & Molecular Biology", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "12", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "28"
      }
    ], 
    "keywords": [
      "large void volume", 
      "solid-state NMR", 
      "molecular dynamics computations", 
      "extramembranous aggregates", 
      "void volume", 
      "key structural features", 
      "asymmetric homodimer", 
      "gauche conformation", 
      "natural products", 
      "molecule interactions", 
      "structural biology", 
      "tail homodimer", 
      "atomistic interactions", 
      "homodimer", 
      "toxic fungicides", 
      "structural features", 
      "minimal unit", 
      "asymmetric head", 
      "assembly", 
      "sponges", 
      "NMR", 
      "yeast", 
      "clathrates", 
      "guests", 
      "biology", 
      "molecules", 
      "conformation", 
      "motif", 
      "AmB", 
      "ergosterol", 
      "fungicides", 
      "interaction", 
      "sterols", 
      "membrane", 
      "dynamics computations", 
      "concert", 
      "aggregates", 
      "products", 
      "mechanism", 
      "lattice", 
      "annealing", 
      "units", 
      "size", 
      "amphotericin B", 
      "volume", 
      "C6-C7", 
      "features", 
      "results", 
      "frontier", 
      "head", 
      "century", 
      "computation"
    ], 
    "name": "Fungicidal amphotericin B sponges are assemblies of staggered asymmetric homodimers encasing large void volumes", 
    "pagination": "972-981", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1143745027"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s41594-021-00685-4"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "34887566"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s41594-021-00685-4", 
      "https://app.dimensions.ai/details/publication/pub.1143745027"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-12-01T06:42", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20221201/entities/gbq_results/article/article_888.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/s41594-021-00685-4"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41594-021-00685-4'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41594-021-00685-4'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41594-021-00685-4'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41594-021-00685-4'


 

This table displays all metadata directly associated to this object as RDF triples.

325 TRIPLES      21 PREDICATES      99 URIs      81 LITERALS      19 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s41594-021-00685-4 schema:about N1c01be7661c04fdfb368c6be45801e87
2 N25f2f46219ea467e87fb4081653564d3
3 N2692e61183e7454ebf899e298081c640
4 N35c6688dabcb4a66b9a6d4b743116d3f
5 N4d5bc8bd3c904798bcb888f3ceba2ee6
6 Nad0acc908adf41ee96de5817e655a6fa
7 Nb247c7e7b9d4452db6c8bef68368753b
8 Nb6be75571aab4ea495dc1b9cb05d8dff
9 Nc89ec6c25c3142e7a3b28e33bac6860d
10 Ncedd632c7de7471293a230dd82da9590
11 Nd575aa8bbdd9497aa68d626388584643
12 Ne27c8b4a63a941028b50e8dd426988b6
13 anzsrc-for:06
14 anzsrc-for:0601
15 schema:author Nce4c9cb90cca439bae96b7613084d91f
16 schema:citation sg:pub.10.1007/bf00533485
17 sg:pub.10.1007/s10858-009-9333-z
18 sg:pub.10.1038/262698a0
19 sg:pub.10.1038/nchembio.1496
20 sg:pub.10.1038/nchembio.663
21 sg:pub.10.1038/nrd.2017.46
22 sg:pub.10.1038/nrm.2017.16
23 sg:pub.10.1038/nsmb.3194
24 sg:pub.10.1038/s41586-019-1018-5
25 sg:pub.10.1186/1758-2946-4-17
26 schema:datePublished 2021-12-09
27 schema:datePublishedReg 2021-12-09
28 schema:description 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.
29 schema:genre article
30 schema:isAccessibleForFree true
31 schema:isPartOf Nc5e24096eb754121af7a6bc5cda31dce
32 Ndf859cf4504e4de1a7decf8a0d1822fa
33 sg:journal.1295033
34 schema:keywords AmB
35 C6-C7
36 NMR
37 aggregates
38 amphotericin B
39 annealing
40 assembly
41 asymmetric head
42 asymmetric homodimer
43 atomistic interactions
44 biology
45 century
46 clathrates
47 computation
48 concert
49 conformation
50 dynamics computations
51 ergosterol
52 extramembranous aggregates
53 features
54 frontier
55 fungicides
56 gauche conformation
57 guests
58 head
59 homodimer
60 interaction
61 key structural features
62 large void volume
63 lattice
64 mechanism
65 membrane
66 minimal unit
67 molecular dynamics computations
68 molecule interactions
69 molecules
70 motif
71 natural products
72 products
73 results
74 size
75 solid-state NMR
76 sponges
77 sterols
78 structural biology
79 structural features
80 tail homodimer
81 toxic fungicides
82 units
83 void volume
84 volume
85 yeast
86 schema:name Fungicidal amphotericin B sponges are assemblies of staggered asymmetric homodimers encasing large void volumes
87 schema:pagination 972-981
88 schema:productId N019dcc95902a4a1084c8488e94083b15
89 N5780976577004c979976f4b11f668617
90 Nd3d035098de34f6a8fc538bc5a508904
91 schema:sameAs https://app.dimensions.ai/details/publication/pub.1143745027
92 https://doi.org/10.1038/s41594-021-00685-4
93 schema:sdDatePublished 2022-12-01T06:42
94 schema:sdLicense https://scigraph.springernature.com/explorer/license/
95 schema:sdPublisher Na942fe5f1c11432e82f6a7078cc78a26
96 schema:url https://doi.org/10.1038/s41594-021-00685-4
97 sgo:license sg:explorer/license/
98 sgo:sdDataset articles
99 rdf:type schema:ScholarlyArticle
100 N019dcc95902a4a1084c8488e94083b15 schema:name pubmed_id
101 schema:value 34887566
102 rdf:type schema:PropertyValue
103 N1c01be7661c04fdfb368c6be45801e87 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
104 schema:name Immunocompromised Host
105 rdf:type schema:DefinedTerm
106 N1ef87af1ba8c4b1db595371891992164 rdf:first sg:person.01260316751.40
107 rdf:rest rdf:nil
108 N25f2f46219ea467e87fb4081653564d3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
109 schema:name Nuclear Magnetic Resonance, Biomolecular
110 rdf:type schema:DefinedTerm
111 N2692e61183e7454ebf899e298081c640 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
112 schema:name Ergosterol
113 rdf:type schema:DefinedTerm
114 N28fb4cf5000e41f8bae1284b86584680 rdf:first sg:person.012547100167.71
115 rdf:rest N50b5c05699804dacadf41ae3dbcf34e1
116 N3227aed107594435b00969b6e33b7dec rdf:first sg:person.0704253111.66
117 rdf:rest N1ef87af1ba8c4b1db595371891992164
118 N35c6688dabcb4a66b9a6d4b743116d3f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
119 schema:name Cells, Cultured
120 rdf:type schema:DefinedTerm
121 N36531b615d334da28d504f9857135a9d rdf:first sg:person.013627312231.29
122 rdf:rest Ncf7e351819a54f389f076c284c05bd25
123 N3e76423595d84ab8812d64762f90e918 rdf:first N6505f5523a3f4d6dbd9460432f3674e4
124 rdf:rest Nd26ea77bbdd44331b9e0116afb32f21e
125 N4a7cfecaab5c4d3188bc401edfed95f5 rdf:first sg:person.013253331401.54
126 rdf:rest N36531b615d334da28d504f9857135a9d
127 N4d5bc8bd3c904798bcb888f3ceba2ee6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
128 schema:name Invasive Fungal Infections
129 rdf:type schema:DefinedTerm
130 N50b5c05699804dacadf41ae3dbcf34e1 rdf:first sg:person.014251054157.38
131 rdf:rest N625cdf13be5b4e02b37a724f89e89493
132 N5780976577004c979976f4b11f668617 schema:name dimensions_id
133 schema:value pub.1143745027
134 rdf:type schema:PropertyValue
135 N625cdf13be5b4e02b37a724f89e89493 rdf:first sg:person.01372371261.09
136 rdf:rest N94c072f6abd24c2ea8f67859e636b44d
137 N6505f5523a3f4d6dbd9460432f3674e4 schema:affiliation grid-institutes:grid.35403.31
138 schema:familyName Holler
139 schema:givenName Jordan T.
140 rdf:type schema:Person
141 N6dd7e6afa91e4372b3fe3f39e87defc3 rdf:first sg:person.01315704334.08
142 rdf:rest Ne2741252afb14890b4ac1c31d94f19d2
143 N94c072f6abd24c2ea8f67859e636b44d rdf:first sg:person.0600437154.42
144 rdf:rest N3e76423595d84ab8812d64762f90e918
145 Na942fe5f1c11432e82f6a7078cc78a26 schema:name Springer Nature - SN SciGraph project
146 rdf:type schema:Organization
147 Nad0acc908adf41ee96de5817e655a6fa schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
148 schema:name Antifungal Agents
149 rdf:type schema:DefinedTerm
150 Nb247c7e7b9d4452db6c8bef68368753b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
151 schema:name Humans
152 rdf:type schema:DefinedTerm
153 Nb6be75571aab4ea495dc1b9cb05d8dff schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
154 schema:name Streptomyces
155 rdf:type schema:DefinedTerm
156 Nc5e24096eb754121af7a6bc5cda31dce schema:volumeNumber 28
157 rdf:type schema:PublicationVolume
158 Nc89ec6c25c3142e7a3b28e33bac6860d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
159 schema:name Molecular Conformation
160 rdf:type schema:DefinedTerm
161 Nce4c9cb90cca439bae96b7613084d91f rdf:first sg:person.013761063555.16
162 rdf:rest N28fb4cf5000e41f8bae1284b86584680
163 Ncedd632c7de7471293a230dd82da9590 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
164 schema:name Cell Membrane
165 rdf:type schema:DefinedTerm
166 Ncf7e351819a54f389f076c284c05bd25 rdf:first sg:person.011205457727.06
167 rdf:rest N6dd7e6afa91e4372b3fe3f39e87defc3
168 Nd26ea77bbdd44331b9e0116afb32f21e rdf:first sg:person.01362440503.25
169 rdf:rest N4a7cfecaab5c4d3188bc401edfed95f5
170 Nd3d035098de34f6a8fc538bc5a508904 schema:name doi
171 schema:value 10.1038/s41594-021-00685-4
172 rdf:type schema:PropertyValue
173 Nd575aa8bbdd9497aa68d626388584643 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
174 schema:name Amphotericin B
175 rdf:type schema:DefinedTerm
176 Ndf859cf4504e4de1a7decf8a0d1822fa schema:issueNumber 12
177 rdf:type schema:PublicationIssue
178 Ne2741252afb14890b4ac1c31d94f19d2 rdf:first sg:person.01046437345.66
179 rdf:rest N3227aed107594435b00969b6e33b7dec
180 Ne27c8b4a63a941028b50e8dd426988b6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
181 schema:name Molecular Dynamics Simulation
182 rdf:type schema:DefinedTerm
183 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
184 schema:name Biological Sciences
185 rdf:type schema:DefinedTerm
186 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
187 schema:name Biochemistry and Cell Biology
188 rdf:type schema:DefinedTerm
189 sg:grant.3859076 http://pending.schema.org/fundedItem sg:pub.10.1038/s41594-021-00685-4
190 rdf:type schema:MonetaryGrant
191 sg:grant.5244336 http://pending.schema.org/fundedItem sg:pub.10.1038/s41594-021-00685-4
192 rdf:type schema:MonetaryGrant
193 sg:grant.6375863 http://pending.schema.org/fundedItem sg:pub.10.1038/s41594-021-00685-4
194 rdf:type schema:MonetaryGrant
195 sg:grant.9534797 http://pending.schema.org/fundedItem sg:pub.10.1038/s41594-021-00685-4
196 rdf:type schema:MonetaryGrant
197 sg:journal.1295033 schema:issn 1545-9993
198 2331-365X
199 schema:name Nature Structural & Molecular Biology
200 schema:publisher Springer Nature
201 rdf:type schema:Periodical
202 sg:person.01046437345.66 schema:affiliation grid-institutes:grid.35403.31
203 schema:familyName Pogorelov
204 schema:givenName Taras V.
205 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01046437345.66
206 rdf:type schema:Person
207 sg:person.011205457727.06 schema:affiliation grid-institutes:grid.35403.31
208 schema:familyName SantaMaria
209 schema:givenName Anna M.
210 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011205457727.06
211 rdf:type schema:Person
212 sg:person.012547100167.71 schema:affiliation grid-institutes:grid.14003.36
213 schema:familyName Soutar
214 schema:givenName Corinne P.
215 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012547100167.71
216 rdf:type schema:Person
217 sg:person.01260316751.40 schema:affiliation grid-institutes:grid.509573.d
218 schema:familyName Rienstra
219 schema:givenName Chad M.
220 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01260316751.40
221 rdf:type schema:Person
222 sg:person.01315704334.08 schema:affiliation grid-institutes:grid.419635.c
223 schema:familyName Schwieters
224 schema:givenName Charles D.
225 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01315704334.08
226 rdf:type schema:Person
227 sg:person.013253331401.54 schema:affiliation grid-institutes:grid.35403.31
228 schema:familyName Khandelwal
229 schema:givenName Anuj
230 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013253331401.54
231 rdf:type schema:Person
232 sg:person.01362440503.25 schema:affiliation grid-institutes:grid.35403.31
233 schema:familyName Hisao
234 schema:givenName Grant S.
235 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01362440503.25
236 rdf:type schema:Person
237 sg:person.013627312231.29 schema:affiliation grid-institutes:grid.35403.31
238 schema:familyName Zhang
239 schema:givenName Jiabao
240 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013627312231.29
241 rdf:type schema:Person
242 sg:person.01372371261.09 schema:affiliation grid-institutes:grid.35403.31
243 schema:familyName Nimerovsky
244 schema:givenName Evgeny
245 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01372371261.09
246 rdf:type schema:Person
247 sg:person.013761063555.16 schema:affiliation grid-institutes:grid.14003.36
248 schema:familyName Lewandowska
249 schema:givenName Agnieszka
250 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013761063555.16
251 rdf:type schema:Person
252 sg:person.014251054157.38 schema:affiliation grid-institutes:grid.35403.31
253 schema:familyName Greenwood
254 schema:givenName Alexander I.
255 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014251054157.38
256 rdf:type schema:Person
257 sg:person.0600437154.42 schema:affiliation grid-institutes:grid.426429.f
258 schema:familyName De Lio
259 schema:givenName Ashley M.
260 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0600437154.42
261 rdf:type schema:Person
262 sg:person.0704253111.66 schema:affiliation grid-institutes:grid.35403.31
263 schema:familyName Burke
264 schema:givenName Martin D.
265 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0704253111.66
266 rdf:type schema:Person
267 sg:pub.10.1007/bf00533485 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015541359
268 https://doi.org/10.1007/bf00533485
269 rdf:type schema:CreativeWork
270 sg:pub.10.1007/s10858-009-9333-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1037424361
271 https://doi.org/10.1007/s10858-009-9333-z
272 rdf:type schema:CreativeWork
273 sg:pub.10.1038/262698a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045561900
274 https://doi.org/10.1038/262698a0
275 rdf:type schema:CreativeWork
276 sg:pub.10.1038/nchembio.1496 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049690615
277 https://doi.org/10.1038/nchembio.1496
278 rdf:type schema:CreativeWork
279 sg:pub.10.1038/nchembio.663 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046204097
280 https://doi.org/10.1038/nchembio.663
281 rdf:type schema:CreativeWork
282 sg:pub.10.1038/nrd.2017.46 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085393524
283 https://doi.org/10.1038/nrd.2017.46
284 rdf:type schema:CreativeWork
285 sg:pub.10.1038/nrm.2017.16 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084129732
286 https://doi.org/10.1038/nrm.2017.16
287 rdf:type schema:CreativeWork
288 sg:pub.10.1038/nsmb.3194 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016142352
289 https://doi.org/10.1038/nsmb.3194
290 rdf:type schema:CreativeWork
291 sg:pub.10.1038/s41586-019-1018-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1112734622
292 https://doi.org/10.1038/s41586-019-1018-5
293 rdf:type schema:CreativeWork
294 sg:pub.10.1186/1758-2946-4-17 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012254507
295 https://doi.org/10.1186/1758-2946-4-17
296 rdf:type schema:CreativeWork
297 grid-institutes:grid.14003.36 schema:alternateName Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA
298 schema:name Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA
299 Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA
300 rdf:type schema:Organization
301 grid-institutes:grid.35403.31 schema:alternateName Carle-Illinois College of Medicine, University of Illinois at Urbana-Champaign, Champaign, IL, USA
302 Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA
303 Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA
304 Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA
305 schema:name Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA
306 Carle-Illinois College of Medicine, University of Illinois at Urbana-Champaign, Champaign, IL, USA
307 Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA
308 Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA
309 Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA
310 National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL, USA
311 School of Chemical Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
312 rdf:type schema:Organization
313 grid-institutes:grid.419635.c schema:alternateName Computational Biomolecular Magnetic Resonance Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
314 schema:name Computational Biomolecular Magnetic Resonance Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
315 rdf:type schema:Organization
316 grid-institutes:grid.426429.f schema:alternateName Computation-based Science and Technology Research Center, The Cyprus Institute, Aglantzia, Cyprus
317 schema:name Computation-based Science and Technology Research Center, The Cyprus Institute, Aglantzia, Cyprus
318 Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA
319 National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL, USA
320 rdf:type schema:Organization
321 grid-institutes:grid.509573.d schema:alternateName Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI, USA
322 schema:name Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA
323 Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI, USA
324 National Magnetic Resonance Facility at Madison, University of Wisconsin-Madison, Madison, WI, USA
325 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...