ArticleLife science alliance2021
Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza.
Article in Life science alliance, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Hepatocyte growth factor activator inhibitor-2 rapidly inactivates airway-expressed human type II transmembrane serine proteases.The Journal of biological chemistry · 2026Article
- Development of ketobenzothiazole-based peptidomimetic TMPRSS13 inhibitors with low nanomolar potency.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Structural basis of TMPRSS11D specificity and autocleavage activation.Nature communications · 2025Article
- From N-0385 to N-0920: Unveiling a Host-Directed Protease Inhibitor with Picomolar Antiviral Efficacy against Prevalent SARS-CoV-2 Variants.Journal of medicinal chemistry · 2025Article
- Molecular Evolution of the H5 and H7 Highly Pathogenic Avian Influenza Virus Haemagglutinin Cleavage Site Motif.Reviews in medical virology · 2025Review
- Development of ketobenzothiazole-based peptidomimetic TMPRSS13 inhibitors with low nanomolar potency.bioRxiv : the preprint server for biology · 2024Article
- Establishment of reverse genetics for genotype VII Newcastle disease virus and altering the cell tropism by inserting TMPRSS2 into the viral genome.Virus genes · 2023Article
- Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2.PLoS pathogens · 2023Article
- Article
- Structural Basis of Covalent Inhibitory Mechanism of TMPRSS2-Related Serine Proteases by Camostat.Journal of virology · 2021Article
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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