WEKO3
アイテム
{"_buckets": {"deposit": "a15b1bc5-2503-4a47-a318-0d5e4adce0f3"}, "_deposit": {"created_by": 2, "id": "218", "owners": [2], "pid": {"revision_id": 0, "type": "depid", "value": "218"}, "status": "published"}, "_oai": {"id": "oai:nagasaki-u.repo.nii.ac.jp:00000218", "sets": ["36"]}, "author_link": ["1000", "995", "992", "996", "997", "994", "990", "999", "1001", "998", "993", "991"], "item_2_biblio_info_6": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2019-06-21", "bibliographicIssueDateType": "Issued"}, "bibliographicIssueNumber": "6", "bibliographicPageStart": "471", "bibliographicVolumeNumber": "10", "bibliographic_titles": [{"bibliographic_title": "Genes"}]}]}, "item_2_description_4": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "Malaria is one of the three major global health threats. Drug development for malaria, especially for its most dangerous \nform caused by Plasmodium falciparum, remains an urgent task due to the emerging drug-resistant parasites. Exploration of novel antimalarial drug targets identified a trifunctional enzyme, malate quinone oxidoreductase (MQO), located in the mitochondrial inner membrane of P. falciparum (PfMQO). PfMQO is involved in the pathways of mitochondrial electron transport chain, tricarboxylic acid cycle, and fumarate cycle.Recent studies have shown that MQO is essential for P. falciparum survival in asexual stage and for the development of experiment cerebral malaria in the murine parasite P. berghei, providing genetic validation of MQO as a drug target. \nHowever, chemical validation of MQO, as a target, remains unexplored. In this study, we used active recombinant protein rPfMQO overexpressed in bacterial membrane fractions to screen a total of 400 compounds from the Pathogen Box, released by Medicines for Malaria Venture. The screening identified seven hit compounds targeting rPfMQO with an IC50 of under 5 μM. We tested the activity of hit compounds against the growth of 3D7 wildtype strain of P. falciparum,among which four compounds showed an IC50 from low to sub-micromolar concentrations, suggesting that PfMQO is indeed a potential antimalarial drug target.", "subitem_description_type": "Abstract"}]}, "item_2_description_63": {"attribute_name": "引用", "attribute_value_mlt": [{"subitem_description": "Genes, 10(6), art.no.471; 2019", "subitem_description_type": "Other"}]}, "item_2_publisher_33": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "MDPI"}]}, "item_2_relation_12": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type": "isIdenticalTo", "subitem_relation_type_id": {"subitem_relation_type_id_text": "10.3390/genes10060471", "subitem_relation_type_select": "DOI"}}]}, "item_2_rights_13": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "c 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)."}]}, "item_2_source_id_8": {"attribute_name": "EISSN", "attribute_value_mlt": [{"subitem_source_identifier": "20734425", "subitem_source_identifier_type": "ISSN"}]}, "item_2_version_type_16": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_version_resource": "http://purl.org/coar/version/c_970fb48d4fbd8a85", "subitem_version_type": "VoR"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Wang, Xinying"}], "nameIdentifiers": [{"nameIdentifier": "990", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Miyazaki, Yukiko"}], "nameIdentifiers": [{"nameIdentifier": "991", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Inaoka, Daniel Ken"}], "nameIdentifiers": [{"nameIdentifier": "992", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Hartuti, Endah Dwi"}], "nameIdentifiers": [{"nameIdentifier": "993", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Watanabe, Yoh-Ichi"}], "nameIdentifiers": [{"nameIdentifier": "994", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Shiba, Tomoo"}], "nameIdentifiers": [{"nameIdentifier": "995", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Harada, Shigeharu"}], "nameIdentifiers": [{"nameIdentifier": "996", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Saimoto, Hiroyuki"}], "nameIdentifiers": [{"nameIdentifier": "997", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Burrows, Jeremy Nicholas"}], "nameIdentifiers": [{"nameIdentifier": "998", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Benito, Francisco Javier Gamo"}], "nameIdentifiers": [{"nameIdentifier": "999", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Nozaki, Tomoyoshi"}], "nameIdentifiers": [{"nameIdentifier": "1000", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kita, Kiyoshi"}], "nameIdentifiers": [{"nameIdentifier": "1001", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2020-12-18"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "Genes10_471.pdf", "filesize": [{"value": "2.2 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": 2200000.0, "url": {"label": "Genes10_471.pdf", "url": "https://nagasaki-u.repo.nii.ac.jp/record/218/files/Genes10_471.pdf"}, "version_id": "af821c1f-f9a8-479b-9e24-4007fd6ec879"}]}, "item_keyword": {"attribute_name": "キーワード", "attribute_value_mlt": [{"subitem_subject": "Drug target", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Energy metabolism", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Inhibitor screening", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Membrane protein", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Mitochondria", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Plasmodium falciparum", "subitem_subject_scheme": "Other"}]}, "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": "Identification of Plasmodium falciparum Mitochondrial Malate: Quinone Oxidoreductase Inhibitors from the Pathogen Box", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Identification of Plasmodium falciparum Mitochondrial Malate: Quinone Oxidoreductase Inhibitors from the Pathogen Box"}]}, "item_type_id": "2", "owner": "2", "path": ["36"], "permalink_uri": "http://hdl.handle.net/10069/39377", "pubdate": {"attribute_name": "公開日", "attribute_value": "2019-08-09"}, "publish_date": "2019-08-09", "publish_status": "0", "recid": "218", "relation": {}, "relation_version_is_last": true, "title": ["Identification of Plasmodium falciparum Mitochondrial Malate: Quinone Oxidoreductase Inhibitors from the Pathogen Box"], "weko_shared_id": -1}
Identification of Plasmodium falciparum Mitochondrial Malate: Quinone Oxidoreductase Inhibitors from the Pathogen Box
http://hdl.handle.net/10069/39377
http://hdl.handle.net/10069/39377ff07f0c4-029e-421e-bd5c-8805c4037b94
名前 / ファイル | ライセンス | アクション |
---|---|---|
Genes10_471.pdf (2.2 MB)
|
|
Item type | 学術雑誌論文 / Journal Article(1) | |||||
---|---|---|---|---|---|---|
公開日 | 2019-08-09 | |||||
タイトル | ||||||
タイトル | Identification of Plasmodium falciparum Mitochondrial Malate: Quinone Oxidoreductase Inhibitors from the Pathogen Box | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Drug target | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Energy metabolism | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Inhibitor screening | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Membrane protein | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Mitochondria | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Plasmodium falciparum | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Wang, Xinying
× Wang, Xinying× Miyazaki, Yukiko× Inaoka, Daniel Ken× Hartuti, Endah Dwi× Watanabe, Yoh-Ichi× Shiba, Tomoo× Harada, Shigeharu× Saimoto, Hiroyuki× Burrows, Jeremy Nicholas× Benito, Francisco Javier Gamo× Nozaki, Tomoyoshi× Kita, Kiyoshi |
|||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Malaria is one of the three major global health threats. Drug development for malaria, especially for its most dangerous form caused by Plasmodium falciparum, remains an urgent task due to the emerging drug-resistant parasites. Exploration of novel antimalarial drug targets identified a trifunctional enzyme, malate quinone oxidoreductase (MQO), located in the mitochondrial inner membrane of P. falciparum (PfMQO). PfMQO is involved in the pathways of mitochondrial electron transport chain, tricarboxylic acid cycle, and fumarate cycle.Recent studies have shown that MQO is essential for P. falciparum survival in asexual stage and for the development of experiment cerebral malaria in the murine parasite P. berghei, providing genetic validation of MQO as a drug target. However, chemical validation of MQO, as a target, remains unexplored. In this study, we used active recombinant protein rPfMQO overexpressed in bacterial membrane fractions to screen a total of 400 compounds from the Pathogen Box, released by Medicines for Malaria Venture. The screening identified seven hit compounds targeting rPfMQO with an IC50 of under 5 μM. We tested the activity of hit compounds against the growth of 3D7 wildtype strain of P. falciparum,among which four compounds showed an IC50 from low to sub-micromolar concentrations, suggesting that PfMQO is indeed a potential antimalarial drug target. |
|||||
書誌情報 |
Genes 巻 10, 号 6, p. 471, 発行日 2019-06-21 |
|||||
出版者 | ||||||
出版者 | MDPI | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 20734425 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.3390/genes10060471 | |||||
権利 | ||||||
権利情報 | c 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Genes, 10(6), art.no.471; 2019 |