The active form of the norovirus RNA-dependent RNA polymerase is a homodimer with cooperative activity
| Autor: | Katrin Jäger, Torsten Unge, Ivonne Robel, Jacques Rohayem, Martin Högbom |
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| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular Protein Conformation viruses Protein Data Bank (RCSB PDB) RNA-dependent RNA polymerase Crystallography X-Ray Virus chemistry.chemical_compound Viral Proteins Protein structure Virology RNA polymerase Binding site Polymerase Binding Sites biology Norovirus RNA-Dependent RNA Polymerase Molecular biology Kinetics chemistry Polynucleotide biology.protein RNA Viral Dimerization |
| Zdroj: | The Journal of general virology. 90(Pt 2) |
| ISSN: | 0022-1317 |
| Popis: | Norovirus (NV) is a leading cause of gastroenteritis worldwide and a major public health concern. So far, the replication strategy of NV remains poorly understood, mainly because of the lack of a cell system to cultivate the virus. In this study, the function and the structure of a key viral enzyme of replication, the RNA-dependent RNA polymerase (RdRp, NS7), was examined. The overall structure of the NV NS7 RdRp was determined by X-ray crystallography to a 2.3 Å (0.23 nm) resolution (PDB ID 2B43), displaying a right-hand fold typical of the template-dependent polynucleotide polymerases. Biochemical analysis evidenced that NV NS7 RdRp is active as a homodimer, with an apparent K d of 0.649 μM and a positive cooperativity (Hill coefficient nH=1.86). Crystals of the NV NS7 homodimer displayed lattices containing dimeric arrangements with high shape complementarity statistics. This experimental data on the structure and function of the NV RdRp may set the cornerstone for the development of polymerase inhibitors to control the infection with NV, a medically relevant pathogen. |
| Databáze: | OpenAIRE |
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