Structural and dynamics characterization of norovirus protease

Daisuke Takahashi, Yasuaki Hiromasa, Yunjeong Kim, Asokan Anbanandam, Xiaolan Yao, Kyeong Ok Chang, Om Prakash

研究成果: ジャーナルへの寄稿記事

14 引用 (Scopus)

抄録

Norovirus protease is an essential enzyme for proteolytic maturation of norovirus nonstructural proteins and has been implicated as a potential target for antiviral drug development. Although X-ray structural studies of the protease give us wealth of structural information including interactions of the protease with its substrate and dimeric overall structure, the role of protein dynamics in the substrate recognition and the biological relevance of the protease dimer remain unclear. Here we determined the solution NMR structure of the 3C-like protease from Norwalk virus (NV 3CLpro), a prototype strain of norovirus, and analyzed its backbone dynamics and hydrodynamic behavior in solution. 15N spin relaxation and analytical ultracentrifugation analyses demonstrate that NV 3CLpro is predominantly a monomer in solution. Solution structure of NV 3CLpro shows significant structural variation in C-terminal domain compared with crystal structures and among lower energy structure ensembles. Also, 15N spin relaxation and Carr-Purcell-Meiboom-Gill (CPMG)-based relaxation dispersion analyses reveal the dynamic properties of residues in the C-terminal domain over a wide range of timescales. In particular, the long loop spanning residues T123-G133 show fast motion (ps-ns), and the residues in the bII-cII region forming the large hydrophobic pocket (S2 site) undergo conformational exchanges on slower timescales (μs-ms), suggesting their important role in substrate recognition.

元の言語英語
ページ(範囲)347-357
ページ数11
ジャーナルProtein Science
22
発行部数3
DOI
出版物ステータス出版済み - 3 1 2013
外部発表Yes

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Norovirus
Peptide Hydrolases
Substrates
Ultracentrifugation
Hydrodynamics
Antiviral Agents
Viruses
Proteins
Dimers
X-Rays
Monomers
Crystal structure
Nuclear magnetic resonance
X rays

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

これを引用

Takahashi, D., Hiromasa, Y., Kim, Y., Anbanandam, A., Yao, X., Chang, K. O., & Prakash, O. (2013). Structural and dynamics characterization of norovirus protease. Protein Science, 22(3), 347-357. https://doi.org/10.1002/pro.2215

Structural and dynamics characterization of norovirus protease. / Takahashi, Daisuke; Hiromasa, Yasuaki; Kim, Yunjeong; Anbanandam, Asokan; Yao, Xiaolan; Chang, Kyeong Ok; Prakash, Om.

:: Protein Science, 巻 22, 番号 3, 01.03.2013, p. 347-357.

研究成果: ジャーナルへの寄稿記事

Takahashi, D, Hiromasa, Y, Kim, Y, Anbanandam, A, Yao, X, Chang, KO & Prakash, O 2013, 'Structural and dynamics characterization of norovirus protease', Protein Science, 巻. 22, 番号 3, pp. 347-357. https://doi.org/10.1002/pro.2215
Takahashi, Daisuke ; Hiromasa, Yasuaki ; Kim, Yunjeong ; Anbanandam, Asokan ; Yao, Xiaolan ; Chang, Kyeong Ok ; Prakash, Om. / Structural and dynamics characterization of norovirus protease. :: Protein Science. 2013 ; 巻 22, 番号 3. pp. 347-357.
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