{"created":"2021-03-01T07:17:27.360888+00:00","id":38286,"links":{},"metadata":{"_buckets":{"deposit":"7d175300-a8d5-47f3-be3e-05420ceeff89"},"_deposit":{"id":"38286","owners":[],"pid":{"revision_id":0,"type":"depid","value":"38286"},"status":"published"},"_oai":{"id":"oai:tsukuba.repo.nii.ac.jp:00038286","sets":["2780:5143","3:62:5595:5173"]},"item_5_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2016-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicPageEnd":"16","bibliographicPageStart":"e00058","bibliographicVolumeNumber":"7","bibliographic_titles":[{"bibliographic_title":"MBIO"}]}]},"item_5_creator_3":{"attribute_name":"著者別名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"ホー, キョン"}],"nameIdentifiers":[{},{},{}]}]},"item_5_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Eukaryal taxa differ with respect to the structure and mechanism of the RNA triphosphatase (RTPase) component of the mRNA capping apparatus. Protozoa, fungi, and certain DNA viruses have a metal-dependent RTPase that belongs to the triphosphate tunnel metalloenzyme (TTM) superfamily. Because the structures, active sites, and chemical mechanisms of the TTM-type RTPases differ from those of mammalian RTPases, the TTM RTPases are potential targets for antiprotozoal, antifungal, and antiviral drug discovery. Here, we employed RNA interference (RNAi) knockdown methods to show that Trypanosoma brucei RTPase Cet1 (TbCet1) is necessary for proliferation of procyclic cells in culture. We then conducted a high-throughput biochemical screen for small-molecule inhibitors of the phosphohydrolase activity of TbCet1. We identified several classes of chemicals-including chlorogenic acids, phenolic glycopyranosides, flavonoids, and other phenolics-that inhibit TbCet1 with nanomolar to low-micromolar 50% inhibitory concentrations (IC50s). We confirmed the activity of these compounds, and tested various analogs thereof, by direct manual assays of TbCet1 phosphohydrolase activity. The most potent nanomolar inhibitors included tetracaffeoylquinic acid, 5-galloylgalloylquinic acid, pentagalloylglucose, rosmarinic acid, and miquelianin. TbCet1 inhibitors were less active (or inactive) against the orthologous TTM-type RTPases of mimivirus, baculovirus, and budding yeast (Saccharomyces cerevisiae). Our results affirm that a TTM RTPase is subject to potent inhibition by small molecules, with the caveat that parallel screens against TTM RTPases from multiple different pathogens may be required to fully probe the chemical space of TTM inhibition.","subitem_description_type":"Abstract"}]},"item_5_publisher_27":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"American Society for Microbiology"}]},"item_5_relation_10":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"26908574","subitem_relation_type_select":"PMID"}}]},"item_5_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1128/mBio.00058-16","subitem_relation_type_select":"DOI"}}]},"item_5_rights_12":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2016 Smith et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Address correspondence to Stewart Shuman, s-shuman@ski.mskcc.org. This article is a direct contribution from a Fellow of the American Academy of Microbiology. External solicited reviewers: Juan Alfonzo, The Ohio State University; Richard Condit, University of Florida."}]},"item_5_select_15":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_select_item":"publisher"}]},"item_5_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"2150-7511","subitem_source_identifier_type":"ISSN"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Smith, Paul"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Ho, C Kiong"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Takagi, Yuko"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Djaballah, Hakim"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Shuman, Stewart"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-06-16"}],"displaytype":"detail","filename":"MB_7-1.pdf","filesize":[{"value":"1.4 MB"}],"format":"application/pdf","licensetype":"license_6","mimetype":"application/pdf","url":{"label":"MB_7-1","url":"https://tsukuba.repo.nii.ac.jp/record/38286/files/MB_7-1.pdf"},"version_id":"df96cd1a-b3d0-4cae-ab77-6c183f8baf03"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Nanomolar Inhibitors of Trypanosoma brucei RNA Triphosphatase.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Nanomolar Inhibitors of Trypanosoma brucei RNA Triphosphatase."}]},"item_type_id":"5","owner":"1","path":["5143","5173"],"pubdate":{"attribute_name":"公開日","attribute_value":"2016-06-16"},"publish_date":"2016-06-16","publish_status":"0","recid":"38286","relation_version_is_last":true,"title":["Nanomolar Inhibitors of Trypanosoma brucei RNA Triphosphatase."],"weko_creator_id":"1","weko_shared_id":5},"updated":"2023-07-12T06:11:54.484881+00:00"}