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Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza
https://repo.qst.go.jp/records/82631
https://repo.qst.go.jp/records/826319a6983a4-9dc5-4260-b26b-ed44d488a2bc
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-04-06 | |||||
| タイトル | ||||||
| タイトル | Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 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 | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Ayako, Ohno
× Ayako, Ohno× 真板宣夫× Takanori, Tabata× Hikaru, Nagano× Kyohei, Arita× Mariko, Ariyoshi× Takayuki, Uchida× Reiko, Nakano× Anayt, Ulla× Kosuke, Sugiura× Koji, Kishimoto× Teshima-Kondo, Shigetada× Yuushi, Okumura× Nobuo, Maita |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Infection of certain influenza viruses is triggered when its HA is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, whereas the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R↓ sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal α-helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19. | |||||
| 書誌情報 |
Life Science Alliance 巻 4, 号 6, p. e202000849, 発行日 2021-04 |
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| 出版者 | ||||||
| 出版者 | Life Science Alliance | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2575-1077 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.26508/lsa.202000849 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.life-science-alliance.org/content/4/6/e202000849 | |||||
