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ID 116821
タイトル別表記
Structure of MSPL–inhibitor complex
著者
Ohno, Ayako Tokushima University|Curreio
真板, 宣夫 Tokushima University|National Institute for Quantum and Radiological Science and Technology KAKEN研究者をさがす
Tabata, Takanori Asahikasei Pharma
Nagano, Hikaru Osaka Prefecture University
Arita, Kyohei Yokohama City University
Ariyoshi, Mariko Osaka University
Ulla, Anayt Tokushima University
奥村, 裕司 Sagami Women’s University KAKEN研究者をさがす
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
Life Science Alliance
ISSN
25751077
出版者
Life Science Alliance
4
6
開始ページ
e202000849
発行日
2021-04-05
権利情報
This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
先端酵素学研究所
医学系
病院
生物資源系