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Structural and Biochemical Analysis of Human Pathogenic Astrovirus Serine Protease at 2.0 angstrom Resolution
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2009 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 387, no 5, 1137-1152 p.Article in journal (Refereed) Published
Abstract [en]

Astroviruses are single-stranded RNA viruses with a replication strategy based on the proteolytic processing of a polyprotein precursor and subsequent release of the viral enzymes of replication. So far, the catalytic properties of the astrovirus protease as well as its structure have remained uncharacterized. In this study, the three-dimensional crystal structure of the predicted protease of human pathogenic astrovirus has been solved to 2.0 angstrom resolution. The protein displays the typical properties of trypsin-like enzymes but also several characteristic features: (i) a catalytic Asp-His-Ser triad in which the aspartate side chain is oriented away from the histidine, being replaced by a water molecule; (ii) a non-common conformation and composition of the SI pocket; and (iii) the lack of the typical surface beta-ribbons together with a "featureless" shape of the substrate-binding site. Hydrolytic activity assays indicate that the S1 pocket recognises Glu and Asp side chains specifically, which, therefore, are predicted to occupy the P1 position on the substrate cleavage site. The positive electrostatic potential featured by the S1 region underlies this specificity. The comparative structural analysis highlights the peculiarity of the astrovirus protease, and differentiates it from the human and viral serine proteases. (C) 2009 Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
2009. Vol. 387, no 5, 1137-1152 p.
Keyword [en]
astrovirus, serine protease, polyprotein, antiviral, catalytic triad
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-129105DOI: 10.1016/j.jmb.2009.02.044ISI: 000265501000009OAI: oai:DiVA.org:uu-129105DiVA: diva2:337587
Available from: 2010-08-06 Created: 2010-08-05 Last updated: 2010-08-06Bibliographically approved

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