Summary information and primary citation
- PDB-id
- 4e7a; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- viral protein, transferase-RNA
- Method
- X-ray (3.0 Å)
- Summary
- Crystal structure of a product state assembly of hcv ns5b genotype 2a jfh-1 isolate with beta hairpin deletion bound to primer-template RNA with a 2',3'-ddc
- Reference
- Mosley RT, Edwards TE, Murakami E, Lam AM, Grice RL, Du J, Sofia MJ, Furman PA, Otto MJ (2012): "Structure of hepatitis C virus polymerase in complex with primer-template RNA." J.Virol., 86, 6503-6511. doi: 10.1128/JVI.00386-12.
- Abstract
- The replication of the hepatitis C viral (HCV) genome is accomplished by the NS5B RNA-dependent RNA polymerase (RdRp), for which mechanistic understanding and structure-guided drug design efforts have been hampered by its propensity to crystallize in a closed, polymerization-incompetent state. The removal of an autoinhibitory β-hairpin loop from genotype 2a HCV NS5B increases de novo RNA synthesis by >100-fold, promotes RNA binding, and facilitated the determination of the first crystallographic structures of HCV polymerase in complex with RNA primer-template pairs. These crystal structures demonstrate the structural realignment required for primer-template recognition and elongation, provide new insights into HCV RNA synthesis at the molecular level, and may prove useful in the structure-based design of novel antiviral compounds. Additionally, our approach for obtaining the RNA primer-template-bound structure of HCV polymerase may be generally applicable to solving RNA-bound complexes for other viral RdRps that contain similar regulatory β-hairpin loops, including bovine viral diarrhea virus, dengue virus, and West Nile virus.
