title: Influenza C virus esterase: analysis of catalytic site, inhibition, and possible function.
abstract: The active site serine of the acetylesterase of influenza C virus was localized to amino acid 71 of the hemagglutinin-esterase protein by affinity labeling with 3H-labeled diisopropylfluorophosphate. This serine and the adjacent amino acids (Phe-Gly-Asp-Ser) are part of a consensus sequence motif found in serine hydrolases. Since comparative analysis failed to reveal esterase sequence similarities with other serine hydrolases, we suggest that this viral enzyme is a serine hydrolase constituting a new family of serine esterases. Furthermore, we found that the influenza C virus esterase was inhibited by isocoumarin derivatives, with 3,4-dichloroisocoumarin being the most potent inhibitor. Addition of this compound prevented elution of influenza C virus from erythrocytes and inhibited virus infectivity, possibly through inhibition of virus entry into cells.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029-6574.
authors.forename: R
authors.initials: R
authors.lastname: Vlasak
authors.forename: T
authors.initials: T
authors.lastname: Muster
authors.forename: A M
authors.initials: AM
authors.lastname: Lauro
authors.forename: J C
authors.initials: JC
authors.lastname: Powers
authors.forename: P
authors.initials: P
authors.lastname: Palese
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002642:Chick Embryo; D003374:Coumarins / Q000037:antagonists & inhibitors; D004912:Erythrocytes / Q000382:microbiology; D004950:Esterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009982:Gammainfluenzavirus / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D007531:Isoflurophate / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D009975:Orthomyxoviridae / Q000201:enzymology*; D011991:Receptors, Virus / Q000378:metabolism; D012694:Serine; D013329:Structure-Activity Relationship; D010948:Viral Plaque Assay
chemical_list: D003374:Coumarins; D011991:Receptors, Virus; D007531:Isoflurophate; D012694:Serine; D004950:Esterases