NS5B

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RNA Dependent RNA Polymerase from Hepatitis C Virus

spinqualitylabelsall models PDB ID 2HAI Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

NS5B is the RNA dependent RNA polymerase of Hepatitis C virus. NS5B, like other RNA dependent RNA polymerases, is error prone, it is approximately a million times lower fidelity than a replicative prokayrotic or eukaryotic DNA polymerase. This is due in part to the fact that NS5B contains no exonuclease or proofreading domain. The proposed mechanism for NS5B polymerization of monomers of RNA triphosphates to extend a primer strand, that may have initiated de novo, is via two divalent cations coordinated by carboxyl groups as seen in DNA polymerases. In the case of NS5B the residues that coordinate divalent cations (Mg2+ or Mn2+ in vitro) are the three

seen here.

Though Hepatitis C virus is of the Flaviviridae family the structure of NS5B is similar to the polymerase of bacteriophage ø 6. Like many template-dependent nucleotide polymerases, NS5B can be visualized similar to a right hand. NS5B contains several , fingers in blue, palm in magenta, thumb in green and a c-terminal domain in yellow. The palm domain contains the active site aspartates.

spinqualitylabelsall models PDB IDs 2HAI (protein) 1RTD (DNA) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

NS5B with B form DNA from HIV Reverse Transcriptase co-crystal model. DNA was modeled in by alignment of palms domain. A beta hairpin (residues 440-455) in the thumb domain has been moved to accommodate DNA, the hairpin is modeled into the minor groove, a possible binding site. Catalytic Mg2+ ions are modeled in green, these would be coordinated by the three aspartic acid carboxylates, (D220, D318 and D319).

The template strand is seen entering through a gap in the fingers domain, incoming nucleotide that extends the primer lines up with the NS5B active site and duplex DNA exits the enzyme through the large central hole. Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.Placeholder, type here.

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Image:PolyProtein.jpg http://www.nature.com/nrmicro/journal/v5/n6/fig_tab/nrmicro1645_F4.html

NS5B + LIGANDS

spinqualitylabelsall models NS5B Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image