S-nitrosothiols as novel, reversible inhibitors of human rhinovirus 3C protease.
Human rhinovirus (HRV) 3C protease was inactivated by a series of S-nitrosothiols. These compounds exhibited different inhibitory activities in a time- and concentration-dependent manner with second-order rate constants (kinact/K(I)) ranging from 131 to 5360 M(-1) min(-1). The inactive enzyme could be re-activated by DTT, GSH and ascorbate, which indicated the inactivation mechanism was through an S-transnitrosylation process.
Xian
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M
Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
Wang
Q M
QM
Chen
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Wang
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Wang
P G
PG
D000086042:3C Viral Proteases; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000187:drug effects*; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008623:Mercaptoethanol; D009603:Nitroso Compounds / Q000737:chemistry / Q000494:pharmacology*; D012229:Rhinovirus / Q000201:enzymology*; D026403:S-Nitrosothiols; D013329:Structure-Activity Relationship; D014764:Viral Proteins
D000998:Antiviral Agents; D015853:Cysteine Proteinase Inhibitors; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D014764:Viral Proteins; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases; D005978:Glutathione; D001205:Ascorbic Acid; D004229:Dithiothreitol