7meq
From Proteopedia
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== Function == | == Function == | ||
[[https://www.uniprot.org/uniprot/TMPS2_HUMAN TMPS2_HUMAN]] Plasma membrane-anchored serine protease that participates in proteolytic cascades of relevance for the normal physiologic function of the prostate (PubMed:25122198). Androgen-induced TMPRSS2 activates several substrates that include pro-hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 leading to extracellular matrix disruption and metastasis of prostate cancer cells (PubMed:15537383, PubMed:26018085, PubMed:25122198). In addition, activates trigeminal neurons and contribute to both spontaneous pain and mechanical allodynia (By similarity).[UniProtKB:Q9JIQ8]<ref>PMID:15537383</ref> <ref>PMID:25122198</ref> <ref>PMID:26018085</ref> (Microbial infection) Facilitates human coronaviruses SARS-CoV and SARS-CoV-2 infections via two independent mechanisms, proteolytic cleavage of ACE2 receptor which promotes viral uptake, and cleavage of coronavirus spike glycoproteins which activates the glycoprotein for host cell entry (PubMed:24227843, PubMed:32142651, PubMed:32404436). Proteolytically cleaves and activates the spike glycoproteins of human coronavirus 229E (HCoV-229E) and human coronavirus EMC (HCoV-EMC) and the fusion glycoproteins F0 of Sendai virus (SeV), human metapneumovirus (HMPV), human parainfluenza 1, 2, 3, 4a and 4b viruses (HPIV). Essential for spread and pathogenesis of influenza A virus (strains H1N1, H3N2 and H7N9); involved in proteolytic cleavage and activation of hemagglutinin (HA) protein which is essential for viral infectivity.<ref>PMID:21068237</ref> <ref>PMID:21325420</ref> <ref>PMID:23536651</ref> <ref>PMID:23966399</ref> <ref>PMID:24027332</ref> <ref>PMID:24227843</ref> <ref>PMID:32142651</ref> <ref>PMID:32404436</ref> | [[https://www.uniprot.org/uniprot/TMPS2_HUMAN TMPS2_HUMAN]] Plasma membrane-anchored serine protease that participates in proteolytic cascades of relevance for the normal physiologic function of the prostate (PubMed:25122198). Androgen-induced TMPRSS2 activates several substrates that include pro-hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 leading to extracellular matrix disruption and metastasis of prostate cancer cells (PubMed:15537383, PubMed:26018085, PubMed:25122198). In addition, activates trigeminal neurons and contribute to both spontaneous pain and mechanical allodynia (By similarity).[UniProtKB:Q9JIQ8]<ref>PMID:15537383</ref> <ref>PMID:25122198</ref> <ref>PMID:26018085</ref> (Microbial infection) Facilitates human coronaviruses SARS-CoV and SARS-CoV-2 infections via two independent mechanisms, proteolytic cleavage of ACE2 receptor which promotes viral uptake, and cleavage of coronavirus spike glycoproteins which activates the glycoprotein for host cell entry (PubMed:24227843, PubMed:32142651, PubMed:32404436). Proteolytically cleaves and activates the spike glycoproteins of human coronavirus 229E (HCoV-229E) and human coronavirus EMC (HCoV-EMC) and the fusion glycoproteins F0 of Sendai virus (SeV), human metapneumovirus (HMPV), human parainfluenza 1, 2, 3, 4a and 4b viruses (HPIV). Essential for spread and pathogenesis of influenza A virus (strains H1N1, H3N2 and H7N9); involved in proteolytic cleavage and activation of hemagglutinin (HA) protein which is essential for viral infectivity.<ref>PMID:21068237</ref> <ref>PMID:21325420</ref> <ref>PMID:23536651</ref> <ref>PMID:23966399</ref> <ref>PMID:24027332</ref> <ref>PMID:24227843</ref> <ref>PMID:32142651</ref> <ref>PMID:32404436</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Transmembrane protease, serine 2 (TMPRSS2) has been identified as key host cell factor for viral entry and pathogenesis of SARS-CoV-2. Specifically, TMPRSS2 proteolytically processes the SARS-CoV-2 Spike (S) protein, enabling virus-host membrane fusion and infection of the airways. We present here a recombinant production strategy for enzymatically active TMPRSS2 and characterization of its matured proteolytic activity, as well as its 1.95 A X-ray cocrystal structure with the synthetic protease inhibitor nafamostat. Our study provides a structural basis for the potent but nonspecific inhibition by nafamostat and identifies distinguishing features of the TMPRSS2 substrate binding pocket that explain specificity. TMPRSS2 cleaved SARS-CoV-2 S protein at multiple sites, including the canonical S1/S2 cleavage site. We ranked the potency of clinical protease inhibitors with half-maximal inhibitory concentrations ranging from 1.4 nM to 120 microM and determined inhibitor mechanisms of action, providing the groundwork for drug development efforts to selectively inhibit TMPRSS2. | ||
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| + | Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation.,Fraser BJ, Beldar S, Seitova A, Hutchinson A, Mannar D, Li Y, Kwon D, Tan R, Wilson RP, Leopold K, Subramaniam S, Halabelian L, Arrowsmith CH, Benard F Nat Chem Biol. 2022 Jun 8. pii: 10.1038/s41589-022-01059-7. doi:, 10.1038/s41589-022-01059-7. PMID:35676539<ref>PMID:35676539</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7meq" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Transmembrane protease serine 2|Transmembrane protease serine 2]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 09:52, 22 June 2022
Crystal structure of human TMPRSS2 in complex with Nafamostat
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