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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.

SUBMITTER: Nakamura K

PROVIDER: S-EPMC1262588 | biostudies-literature | 2005 Nov

REPOSITORIES: biostudies-literature

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A norovirus protease structure provides insights into active and substrate binding site integrity.

Nakamura Kentaro K Someya Yuichi Y Kumasaka Takashi T Ueno Go G Yamamoto Masaki M Sato Takao T Takeda Naokazu N Miyamura Tatsuo T Tanaka Nobuo N

Journal of virology 20051101 21

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 ...[more]

PMID: 16227288

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A structural study of norovirus 3C protease specificity: binding of a designed active site-directed peptide inhibitor.

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