Conformational flexibility of the dengue virus RNA-Dependent RNA polymerase revealed by a complex with an inhibitor

Christian G. Noble, Siew Pheng Lim, Yen Liang Chen, Chong Wai Liew, Lijian Yap, Julien Lescar, Pei-Yong Shi

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

We report a highly reproducible method to crystallize the RNA-dependent RNA polymerase (RdRp) domain of dengue virus serotype 3 (DENV-3), allowing structure refinement to a 1.79-å resolution and revealing amino acids not seen previously. We also present a DENV-3 polymerase/inhibitor cocrystal structure at a 2.1-å resolution. The inhibitor binds to the RdRp as a dimer and causes conformational changes in the protein. The improved crystallization conditions and new structural information should accelerate structure-based drug discovery.

Original languageEnglish (US)
Pages (from-to)5291-5295
Number of pages5
JournalJournal of Virology
Volume87
Issue number9
DOIs
StatePublished - May 2013
Externally publishedYes

Fingerprint

RNA-directed RNA polymerase
RNA Replicase
Dengue virus
Dengue Virus
Drug Discovery
crystallization
Crystallization
Amino Acids
drugs
amino acids
Proteins
proteins
Serogroup
methodology

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Conformational flexibility of the dengue virus RNA-Dependent RNA polymerase revealed by a complex with an inhibitor. / Noble, Christian G.; Lim, Siew Pheng; Chen, Yen Liang; Liew, Chong Wai; Yap, Lijian; Lescar, Julien; Shi, Pei-Yong.

In: Journal of Virology, Vol. 87, No. 9, 05.2013, p. 5291-5295.

Research output: Contribution to journalArticle

Noble, Christian G. ; Lim, Siew Pheng ; Chen, Yen Liang ; Liew, Chong Wai ; Yap, Lijian ; Lescar, Julien ; Shi, Pei-Yong. / Conformational flexibility of the dengue virus RNA-Dependent RNA polymerase revealed by a complex with an inhibitor. In: Journal of Virology. 2013 ; Vol. 87, No. 9. pp. 5291-5295.
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