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Title: A multi-step strategy to obtain crystals of the dengue virus RNA-dependent RNA polymerase that diffract to high resolution

Journal Article · · Acta Crystallographica. Section F
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  1. Novartis Institute for Tropical Diseases, 10 Biopolis Road, Chromos Building, Singapore 138670 (Singapore)

Crystals of the RNA-dependent RNA polymerase catalytic domain from the dengue virus NS5 protein have been obtained using a strategy that included expression screening of naturally occurring serotype variants of the protein, the addition of divalent metal ions and crystal dehydration. These crystals diffract to 1.85 Å resolution and are thus suitable for a structure-based drug-design program. Dengue virus, a member of the Flaviviridae genus, causes dengue fever, an important emerging disease with several million infections occurring annually for which no effective therapy exists. The viral RNA-dependent RNA polymerase NS5 plays an important role in virus replication and represents an interesting target for the development of specific antiviral compounds. Crystals that diffract to 1.85 Å resolution that are suitable for three-dimensional structure determination and thus for a structure-based drug-design program have been obtained using a strategy that included expression screening of naturally occurring serotype variants of the protein, the addition of divalent metal ions and crystal dehydration.

OSTI ID:
22360256
Journal Information:
Acta Crystallographica. Section F, Vol. 63, Issue Pt 2; Other Information: PMCID: PMC2330120; PMID: 17277444; PUBLISHER-ID: en5214; OAI: oai:pubmedcentral.nih.gov:2330120; Copyright (c) International Union of Crystallography 2007; Country of input: International Atomic Energy Agency (IAEA); ISSN 1744-3091
Country of Publication:
United Kingdom
Language:
English