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

doi:10.1128/JVI.00045-13

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 journal › Article › peer-review

71 Scopus citations

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 language	English (US)
Pages (from-to)	5291-5295
Number of pages	5
Journal	Journal of virology
Volume	87
Issue number	9
DOIs	https://doi.org/10.1128/JVI.00045-13
State	Published - May 2013
Externally published	Yes

ASJC Scopus subject areas

Microbiology
Immunology
Insect Science
Virology

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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-{\aa} resolution and revealing amino acids not seen previously. We also present a DENV-3 polymerase/inhibitor cocrystal structure at a 2.1-{\aa} 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.",

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AU - Lim, Siew Pheng

AU - Chen, Yen Liang

AU - Liew, Chong Wai

AU - Yap, Lijian

AU - Lescar, Julien

AU - Shi, Pei Yong

PY - 2013/5

Y1 - 2013/5

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AB - 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.

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

Abstract

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