Selected article for: "crystal structure and homology model"
Author: Ohno, Ayako; Maita, Nobuo; Tabata, Takanori; Nagano, Hikaru; Arita, Kyohei; Ariyoshi, Mariko; Uchida, Takayuki; Nakao, Reiko; Ulla, Anayt; Sugiura, Kosuke; Kishimoto, Koji; Teshima-Kondo, Shigetada; Okumura, Yuushi; Nikawa, Takeshi
Title: Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza
  • Cord-id: y15t8s5a
  • Document date: 2021_4_5
    • ID: y15t8s5a
    Snippet: 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 s
    Document: 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.

    Search related documents:
    Co phrase search for related documents
    • activate cleavage and acute sars cov respiratory syndrome coronavirus: 1
    • activation cleavage and acute sars cov respiratory syndrome coronavirus: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13
    • activation cleavage and additional insertion: 1
    • activation motif and acute sars cov respiratory syndrome coronavirus: 1
    • activation motif and low density: 1
    • active form and acute sars cov respiratory syndrome coronavirus: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16
    • active form and low density: 1
    • active form and low density lipoprotein: 1
    • active site and acute sars cov respiratory syndrome coronavirus: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25
    • active site and loop region: 1, 2, 3, 4, 5, 6
    • active site and low density: 1
    • active site and low density lipoprotein: 1
    • active site form and acute sars cov respiratory syndrome coronavirus: 1, 2, 3, 4, 5, 6, 7
    • acute sars cov respiratory syndrome coronavirus and loop region: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
    • acute sars cov respiratory syndrome coronavirus and low density: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18
    • acute sars cov respiratory syndrome coronavirus and low density lipoprotein: 1, 2, 3, 4, 5, 6, 7, 8
    • acute sars cov respiratory syndrome coronavirus and low density lipoprotein receptor: 1
    • loop region and low density: 1