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Home / Equine Research Bank / Structure / The crystal structure of the Venezuelan equine encephalitis ...
Structure (London, England : 1993)2006; 14(9); 1449-1458; doi: 10.1016/j.str.2006.07.010

The crystal structure of the Venezuelan equine encephalitis alphavirus nsP2 protease.

Abstract: Alphavirus replication and propagation is dependent on the protease activity of the viral nsP2 protein, which cleaves the nsP1234 polyprotein replication complex into functional components. Thus, nsP2 is an attractive target for drug discovery efforts to combat highly pathogenic alphaviruses. Unfortunately, antiviral development has been hampered by a lack of structural information for the nsP2 protease. Here, we report the crystal structure of the nsP2 protease (nsP2pro) from Venezuelan equine encephalitis alphavirus determined at 2.45 A resolution. The protease structure consists of two distinct domains. The nsP2pro N-terminal domain contains the catalytic dyad cysteine and histidine residues organized in a protein fold that differs significantly from any known cysteine protease or protein folds. The nsP2pro C-terminal domain displays structural similarity to S-adenosyl-L-methionine-dependent RNA methyltransferases and provides essential elements that contribute to substrate recognition and may also regulate the structure of the substrate binding cleft.
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Publication Date: 2006-09-12 PubMed ID: 16962975DOI: 10.1016/j.str.2006.07.010Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article presents the crystal structure of the nsP2 protease, a crucial component of the Venezuelan equine encephalitis alphavirus, which is important for antiviral drug discovery aimed at alphaviruses.

Alphavirus Replication and Propagation

  • The replication and propagation of alphaviruses are dependent on the proteolytic activity of the viral nsP2 protein.
  • The nsP2 protein cleaves the nsP1234 polyprotein replication complex into functional components, essentially playing a key role in the virus’s life cycle.

Importance of nsP2 in Drug Discovery

  • The unique role of nsP2 in the functioning of alphaviruses makes it an attractive target for antiviral drug discovery efforts.
  • By inhibiting or manipulating the function of nsP2, the replication and propagation of the virus could be controlled or stopped altogether.
  • However, the lack of structural information about nsP2 protease has been a hindrance to the development of antivirals that target it.

Crystal Structure of nsP2 Protease

  • In this study, the researchers have determined the crystal structure of the nsP2 protease from Venezuelan equine encephalitis alphavirus at a resolution of 2.45 A.
  • The protease structure consists of two distinct domains: the N-terminal domain and the C-terminal domain.
  • The N-terminal domain contains a unique protein fold and catalytic dyad made of cysteine and histidine residues, which are considerably different from any known cysteine protease or protein folds.
  • The C-terminal domain of nsP2pro showcases structural similarity to S-adenosyl-L-methionine-dependent RNA methyltransferases, which are molecules involved in regulating gene expression.
  • Some features of the C-terminal domain contribute to substrate recognition and might influence the structure of the substrate binding cleft. This could be integral to understanding how to disrupt the virus’s life cycle with antiviral drugs.

Cite This Article

APA
Russo AT, White MA, Watowich SJ. (2006). The crystal structure of the Venezuelan equine encephalitis alphavirus nsP2 protease. Structure, 14(9), 1449-1458. https://doi.org/10.1016/j.str.2006.07.010

Publication

Structure (London, England : 1993)
ISSN: 0969-2126
NlmUniqueID: 101087697
Country: United States
Language: English
Volume: 14
Issue: 9
Pages: 1449-1458

Researcher Affiliations

Russo, Andrew T
  • Department of Biochemistry and Molecular Biology and Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, Galveston, Texas 77555, USA.
White, Mark A
    Watowich, Stanley J

      MeSH Terms

      • Amino Acid Sequence
      • Catalytic Domain
      • Crystallography, X-Ray
      • Cysteine Endopeptidases / chemistry
      • Cysteine Endopeptidases / metabolism
      • Encephalitis Virus, Venezuelan Equine / enzymology
      • Hydrolysis
      • Models, Molecular
      • Molecular Sequence Data
      • Protein Conformation
      • Sequence Homology, Amino Acid

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