Tetrahydrocarbazoles are a novel class of potent P-type ATPase inhibitors with antifungal activity
Publication Date
January 02, 2018
Authors
Maike Bublitz, Lasse Kjellerup, Karen O’hanlon Cohrt, Sandra Gordon, et al
Volume
13
Issue
1
Pages
e0188620
DOI
https://dx.plos.org/10.1371/journal.pone.0188620
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0188620
Scopus
85040007611
Mendeley
http://www.mendeley.com/research/tetrahydrocarbazoles-novel-class-potent-ptype-atpase-inhibitors-antifungal-activity
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Tetrahydrocarbazoles are a novel class of potent P-type ATPase inhibitors with antifungal activity", "type"=>"journal", "authors"=>[{"first_name"=>"Maike", "last_name"=>"Bublitz", "scopus_author_id"=>"23972140100"}, {"first_name"=>"Lasse", "last_name"=>"Kjellerup", "scopus_author_id"=>"56211059900"}, {"first_name"=>"Karen O.Hanlon", "last_name"=>"Cohrt", "scopus_author_id"=>"57194679271"}, {"first_name"=>"Sandra", "last_name"=>"Gordon", "scopus_author_id"=>"57194688901"}, {"first_name"=>"Anne Louise", "last_name"=>"Mortensen", "scopus_author_id"=>"57200168952"}, {"first_name"=>"Johannes D.", "last_name"=>"Clausen", "scopus_author_id"=>"56563591200"}, {"first_name"=>"Thomas David", "last_name"=>"Pallin", "scopus_author_id"=>"36866136000"}, {"first_name"=>"John Bondo", "last_name"=>"Hansen", "scopus_author_id"=>"57199437177"}, {"first_name"=>"Anja Thoe", "last_name"=>"Fuglsang", "scopus_author_id"=>"7003385103"}, {"first_name"=>"William", "last_name"=>"Dalby-Brown", "scopus_author_id"=>"8337016000"}, {"first_name"=>"Anne Marie L.", "last_name"=>"Winther", "scopus_author_id"=>"57195622829"}], "year"=>2018, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-85040007611", "pui"=>"620020449", "doi"=>"10.1371/journal.pone.0188620", "isbn"=>"1111111111", "sgr"=>"85040007611", "pmid"=>"29293507"}, "id"=>"421cd26a-082b-33cd-bd54-437aea5e8eb5", "abstract"=>"We have identified a series of tetrahydrocarbazoles as novel P-type ATPase inhibitors. Using a set of rationally designed analogues, we have analyzed their structure-activity relationship using functional assays, crystallographic data and computational modeling. We found that tetrahydrocarbazoles inhibit adenosine triphosphate (ATP) hydrolysis of the fungal H+-ATPase, depolarize the fungal plasma membrane and exhibit broad-spectrum antifungal activity. Comparative inhibition studies indicate that many tetrahydrocarbazoles also inhibit the mammalian Ca2+-ATPase (SERCA) and Na+,K+-ATPase with an even higher potency than Pma1. We have located the binding site for this compound class by crystallographic structure determination of a SERCA-tetrahydrocarbazole complex to 3.0 Å resolution, finding that the compound binds to a region above the ion inlet channel of the ATPase. A homology model of the Candida albicans H+-ATPase based on this crystal structure, indicates that the compounds could bind to the same pocket and identifies pocket extensions that could be exploited for selectivity enhancement. The results of this study will aid further optimization towards selective H+-ATPase inhibitors as a new class of antifungal agents.", "link"=>"http://www.mendeley.com/research/tetrahydrocarbazoles-novel-class-potent-ptype-atpase-inhibitors-antifungal-activity", "reader_count"=>8, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>2, "Researcher"=>2, "Student > Postgraduate"=>1, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>2, "Researcher"=>2, "Student > Postgraduate"=>1, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>5, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}}, "group_count"=>0}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/85040007611"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/85040007611?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85040007611&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85040007611&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/85040007611", "dc:identifier"=>"SCOPUS_ID:85040007611", "eid"=>"2-s2.0-85040007611", "dc:title"=>"Tetrahydrocarbazoles are a novel class of potent P-type ATPase inhibitors with antifungal activity", "dc:creator"=>"Bublitz M.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"13", "prism:issueIdentifier"=>"1", "prism:pageRange"=>nil, "prism:coverDate"=>"2018-01-01", "prism:coverDisplayDate"=>"January 2018", "prism:doi"=>"10.1371/journal.pone.0188620", "citedby-count"=>"6", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"University of Oxford Medical Sciences Division", "affiliation-city"=>"Oxford", "affiliation-country"=>"United Kingdom"}], "pubmed-id"=>"29293507", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e0188620", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Twitter

Counter

  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"142", "xml_views"=>"9", "html_views"=>"391"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"37", "xml_views"=>"1", "html_views"=>"80"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"24", "xml_views"=>"2", "html_views"=>"63"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"28", "xml_views"=>"1", "html_views"=>"53"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"25", "xml_views"=>"6", "html_views"=>"47"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"23", "xml_views"=>"7", "html_views"=>"60"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"31", "xml_views"=>"3", "html_views"=>"23"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"12", "xml_views"=>"2", "html_views"=>"18"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"29", "xml_views"=>"1", "html_views"=>"25"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"26", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"25", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"21"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"22", "xml_views"=>"1", "html_views"=>"28"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"11", "year"=>"2019", "pdf_views"=>"16", "xml_views"=>"4", "html_views"=>"28"}
  • {"month"=>"12", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"1", "year"=>"2020", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"2", "year"=>"2020", "pdf_views"=>"20", "xml_views"=>"2", "html_views"=>"30"}
  • {"month"=>"3", "year"=>"2020", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"4", "year"=>"2020", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"5", "year"=>"2020", "pdf_views"=>"47", "xml_views"=>"1", "html_views"=>"12"}
  • {"month"=>"6", "year"=>"2020", "pdf_views"=>"31", "xml_views"=>"1", "html_views"=>"16"}
  • {"month"=>"7", "year"=>"2020", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"14"}
  • {"month"=>"8", "year"=>"2020", "pdf_views"=>"24", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"9", "year"=>"2020", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"10", "year"=>"2020", "pdf_views"=>"25", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"11", "year"=>"2020", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"9"}

PMC Usage Stats

  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"2", "full-text"=>"0", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"2"}
  • {"unique-ip"=>"38", "full-text"=>"55", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"17", "full-text"=>"16", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"12", "full-text"=>"8", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"19", "full-text"=>"16", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"20", "full-text"=>"23", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"18", "full-text"=>"19", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"15", "full-text"=>"15", "pdf"=>"21", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"17", "full-text"=>"30", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"20", "full-text"=>"20", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"12", "full-text"=>"14", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"20", "full-text"=>"17", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"19", "full-text"=>"17", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"12", "full-text"=>"13", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"13", "full-text"=>"11", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"12", "full-text"=>"14", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"15", "full-text"=>"11", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"7"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"15", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"9"}
  • {"unique-ip"=>"7", "full-text"=>"4", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2020", "month"=>"10"}
Loading … Spinner
There are currently no alerts