The Crystal Structure of the Venezuelan Equine Encephalitis Alphavirus nsP2 Protease

Andrew T. Russo, Mark White, Stanley Watowich

Research output: Contribution to journalArticle

66 Citations (Scopus)

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 Å 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.

Original languageEnglish (US)
Pages (from-to)1449-1458
Number of pages10
JournalStructure
Volume14
Issue number9
DOIs
StatePublished - Sep 2006

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Venezuelan Equine Encephalomyelitides
Alphavirus
Peptide Hydrolases
Polyproteins
S-Adenosylmethionine
Cysteine Proteases
Methyltransferases
Viral Proteins
Drug Discovery
Histidine
Antiviral Agents
Cysteine
Catalytic Domain
Proteins
RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

The Crystal Structure of the Venezuelan Equine Encephalitis Alphavirus nsP2 Protease. / Russo, Andrew T.; White, Mark; Watowich, Stanley.

In: Structure, Vol. 14, No. 9, 09.2006, p. 1449-1458.

Research output: Contribution to journalArticle

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