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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

Abstract

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.

Authors:
 [1];  [2]; ; ; ;  [1];  [1];  [2]
  1. Novartis Institute for Tropical Diseases, 10 Biopolis Road, Chromos Building, Singapore 138670 (Singapore)
  2. (Singapore)
Publication Date:
OSTI Identifier:
22360256
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section F; Journal Volume: 63; Journal 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)
Country of Publication:
United Kingdom
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; CRYSTALS; DEHYDRATION; DESIGN; IONS; METALS; RESOLUTION; SCREENING

Citation Formats

Yap, Thai Leong, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Chen, Yen Liang, Xu, Ting, Wen, Daying, Vasudevan, Subhash G., Lescar, Julien, E-mail: julien@ntu.edu.sg, and School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551. A multi-step strategy to obtain crystals of the dengue virus RNA-dependent RNA polymerase that diffract to high resolution. United Kingdom: N. p., 2007. Web. doi:10.1107/S1744309106055084.
Yap, Thai Leong, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Chen, Yen Liang, Xu, Ting, Wen, Daying, Vasudevan, Subhash G., Lescar, Julien, E-mail: julien@ntu.edu.sg, & School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551. A multi-step strategy to obtain crystals of the dengue virus RNA-dependent RNA polymerase that diffract to high resolution. United Kingdom. doi:10.1107/S1744309106055084.
Yap, Thai Leong, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Chen, Yen Liang, Xu, Ting, Wen, Daying, Vasudevan, Subhash G., Lescar, Julien, E-mail: julien@ntu.edu.sg, and School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551. Thu . "A multi-step strategy to obtain crystals of the dengue virus RNA-dependent RNA polymerase that diffract to high resolution". United Kingdom. doi:10.1107/S1744309106055084.
@article{osti_22360256,
title = {A multi-step strategy to obtain crystals of the dengue virus RNA-dependent RNA polymerase that diffract to high resolution},
author = {Yap, Thai Leong and School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 and Chen, Yen Liang and Xu, Ting and Wen, Daying and Vasudevan, Subhash G. and Lescar, Julien, E-mail: julien@ntu.edu.sg and School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551},
abstractNote = {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.},
doi = {10.1107/S1744309106055084},
journal = {Acta Crystallographica. Section F},
number = Pt 2,
volume = 63,
place = {United Kingdom},
year = {Thu Feb 01 00:00:00 EST 2007},
month = {Thu Feb 01 00:00:00 EST 2007}
}