title: A norovirus protease structure provides insights into active and substrate binding site integrity.
abstract: Norovirus 3C-like proteases are crucial to proteolytic processing of norovirus polyproteins. We determined the crystal structure of the 3C-like protease from Chiba virus, a norovirus, at 2.8-A resolution. An active site including Cys139 and His30 is present, as is a hydrogen bond network that stabilizes the active site conformation. In the oxyanion hole backbone, a structural difference was observed probably upon substrate binding. A peptide substrate/enzyme model shows that several interactions between the two components are critical for substrate binding and that the S1 and S2 sites appropriately accommodate the substrate P1 and P2 residues, respectively. Knowledge of the structure and a previous mutagenesis study allow us to correlate proteolysis and structure.
authors.affiliation: Department of Life Science, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nakamura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Someya
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumasaka
authors.forename: Go
authors.initials: G
authors.lastname: Ueno
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Takao
authors.initials: T
authors.lastname: Sato
authors.forename: Naokazu
authors.initials: N
authors.lastname: Takeda
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Miyamura
authors.forename: Nobuo
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D000086042:3C Viral Proteases; D000595:Amino Acid Sequence; D001665:Binding Sites; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D029322:Norovirus / Q000201:enzymology*; D020836:Protein Structure, Quaternary; D016415:Sequence Alignment; D013379:Substrate Specificity; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases