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ID 116821
Title Alternative
Structure of MSPL–inhibitor complex
Author
Ohno, Ayako Tokushima University|Curreio
Maita, Nobuo Tokushima University|National Institute for Quantum and Radiological Science and Technology KAKEN Search Researchers
Tabata, Takanori Asahikasei Pharma
Nagano, Hikaru Osaka Prefecture University
Arita, Kyohei Yokohama City University
Ariyoshi, Mariko Osaka University
Ulla, Anayt Tokushima University
Okumura, Yuushi Sagami Women’s University KAKEN Search Researchers
Content Type
Journal Article
Description
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.
Journal Title
Life Science Alliance
ISSN
25751077
Publisher
Life Science Alliance
Volume
4
Issue
6
Start Page
e202000849
Published Date
2021-04-05
Rights
This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
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DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences
Medical Sciences
University Hospital
Bioscience and Bioindustry