2hwk Citations

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

Structure 14 1449-58 (2006)
Cited: 55 times
EuropePMC logo PMID: 16962975

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.

Reviews - 2hwk mentioned but not cited (2)

Articles - 2hwk mentioned but not cited (8)

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Reviews citing this publication (7)

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Articles citing this publication (38)

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Related citations provided by authors (1)

  1. Structural Basis of Substrate Specificity in Venezuelan Equine Encephalitis nsP2 Protease. Russo AT, White MA, Malmstrom R, Watowich SJ To be published -