Structural and inhibitor studies of norovirus 3C-like proteases

Daisuke Takahashi, Yunjeong Kim, Scott Lovell, Om Prakash, William C. Groutas, Kyeong Ok Chang

研究成果: ジャーナルへの寄稿記事

16 引用 (Scopus)

抄録

Noroviruses have a single-stranded, positive sense 7-8. kb RNA genome, which encodes a polyprotein precursor processed by a virus-encoded 3C-like cysteine protease (3CLpro) to generate mature non-structural proteins. Because processing of the polyprotein is essential for virus replication, norovirus 3CLpro has been targeted for the discovery of anti-norovirus small molecule therapeutics. Thus, we performed functional, structural and inhibition studies of norovirus 3CLpro with fluorescence resonance energy transfer (FRET) assay, X-ray crystallography, and NMR spectroscopy with a synthetic protease inhibitor. Three 3CLpro from Norwalk virus (NV, genogroup I), MD145 (genogroup II) and murine norovirus-1 (MNV-1, genogroup V) were optimized for a FRET assay, and compared for the inhibitory activities of a synthetic protease inhibitor (GC376). The apo 3D structures of NV 3CLpro determined with X-ray crystallography and NMR spectroscopy were further analyzed. In addition, the binding mode of NV 3CLpro-GC376 was compared with X-ray crystallography and NMR spectroscopy. The results of this report provide insight into the interaction of NV 3CLpro with substrate/inhibitor for better understanding of the enzyme and antiviral drug development.

元の言語英語
ページ(範囲)437-444
ページ数8
ジャーナルVirus Research
178
発行部数2
DOI
出版物ステータス出版済み - 12 26 2013
外部発表Yes

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Norovirus
Cysteine Proteases
X Ray Crystallography
Polyproteins
Fluorescence Resonance Energy Transfer
Magnetic Resonance Spectroscopy
Genotype
Protease Inhibitors
Norwalk virus
Virus Replication
3C proteases
Antiviral Agents
Genome
RNA
Viruses
Enzymes

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Virology
  • Infectious Diseases

これを引用

Takahashi, D., Kim, Y., Lovell, S., Prakash, O., Groutas, W. C., & Chang, K. O. (2013). Structural and inhibitor studies of norovirus 3C-like proteases. Virus Research, 178(2), 437-444. https://doi.org/10.1016/j.virusres.2013.09.008

Structural and inhibitor studies of norovirus 3C-like proteases. / Takahashi, Daisuke; Kim, Yunjeong; Lovell, Scott; Prakash, Om; Groutas, William C.; Chang, Kyeong Ok.

:: Virus Research, 巻 178, 番号 2, 26.12.2013, p. 437-444.

研究成果: ジャーナルへの寄稿記事

Takahashi, D, Kim, Y, Lovell, S, Prakash, O, Groutas, WC & Chang, KO 2013, 'Structural and inhibitor studies of norovirus 3C-like proteases', Virus Research, 巻. 178, 番号 2, pp. 437-444. https://doi.org/10.1016/j.virusres.2013.09.008
Takahashi, Daisuke ; Kim, Yunjeong ; Lovell, Scott ; Prakash, Om ; Groutas, William C. ; Chang, Kyeong Ok. / Structural and inhibitor studies of norovirus 3C-like proteases. :: Virus Research. 2013 ; 巻 178, 番号 2. pp. 437-444.
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