{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:27:00Z","timestamp":1791278820840,"version":"4.1.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1990,11]]},"abstract":"<jats:p>Sequence homology and molecular modeling studies have suggested that the N-terminal one-third of the flavirvirus nonstructural protein NS3 functions as a trypsin-like serine protease. To examine the putative proteolytic activity of NS3, segments of the yellow fever virus genome were subcloned into plasmid transcription\/translation vectors and cell-free translation products were characterized. The results suggest that a protease activity encoded within NS2B and the N-terminal one-third of yellow fever virus NS3 is capable of cis-acting site-specific proteolysis at the NS2B-NS3 cleavage site and dilution-insensitive cleavage of the NS2A-NS2B site. Site-directed mutagenesis of the His-53, Asp-77, and Ser-138 residues of NS3 that compose the proposed catalytic triad implicates this domain as a serine protease. Infectious virus was not recovered from mammalian cells transfected with RNAs transcribed from full-length yellow fever virus cDNA templates containing mutations at Ser-138 (which abolish or dramatically reduce protease activity in vitro), suggesting that the protease is required for viral replication.<\/jats:p>","DOI":"10.1073\/pnas.87.22.8898","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T07:30:16Z","timestamp":1149060616000},"page":"8898-8902","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":281,"title":["Evidence that the N-terminal domain of nonstructural protein NS3 from yellow fever virus is a serine protease responsible for site-specific cleavages in the viral polyprotein."],"prefix":"10.1073","volume":"87","author":[{"given":"T J","family":"Chambers","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110-1093."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R C","family":"Weir","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110-1093."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Grakoui","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110-1093."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D W","family":"McCourt","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110-1093."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J F","family":"Bazan","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110-1093."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R J","family":"Fletterick","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110-1093."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C M","family":"Rice","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110-1093."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1990,11]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.87.22.8898","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:14:07Z","timestamp":1649855647000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.87.22.8898"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1990,11]]},"references-count":0,"journal-issue":{"issue":"22","published-print":{"date-parts":[[1990,11]]}},"alternative-id":["10.1073\/pnas.87.22.8898"],"URL":"https:\/\/doi.org\/10.1073\/pnas.87.22.8898","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1990,11]]},"assertion":[{"value":"1990-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}