NS5B

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Revision as of 00:07, 21 April 2009

RNA Dependent RNA Polymerase from Hepatitis C Virus

NS5B is the RNA dependent RNA polymerase of Hepatitis C virus. NS5B, like other RNA dependent RNA polymerases, is error prone, this viral RNA replicase is of 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. The similarity to the bacteriophage polymerase is due to NS5B containing a fully encircled active site. 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 and there are several contacts between the fingers and thumbs domain that give the active site an encircled structure. There is a that is proposed to move upon formation of exiting double stranded RNA.

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.

Image:PolyProtein.jpg Figure 4. http://www.nature.com/nrmicro/journal/v5/n6/fig_tab/nrmicro1645_F4.html

NS5B + LIGANDS

Figure 5. NS5B in complex with ligands from deposited structures all superimposed on the 1.58Å resolution 2HAI. Ligands are from

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

Nicolas Villanueva, Alexander Berchansky, Kody Witham, Michal Harel, David Canner

Retrieved from "http://52.214.119.220/wiki/index.php/NS5B"

@@ Line 2: / Line 2: @@
-<applet load='2HAI_catalytic3.pdb' size='400' frame='true' align='right' caption='PDB ID 2HAI' />NS5B is the RNA dependent RNA polymerase of Hepatitis C virus. NS5B, like other RNA dependent RNA polymerases, is error prone, this viral RNA replicase is of 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
+<applet load='2HAI_catalytic3.pdb' size='400' frame='true' align='right' caption='Figure 1. PDB ID 2HAI' />NS5B is the RNA dependent RNA polymerase of Hepatitis C virus. NS5B, like other RNA dependent RNA polymerases, is error prone, this viral RNA replicase is of 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
 <scene name='NS5B/Native_ns5b/4'>active site aspartates (220, 318 and 319)</scene> seen here.
@@ Line 9: / Line 9: @@
 <scene name='NS5B/Native_ns5b/6'>Beta-hairpin in thumb domain</scene> that is proposed to move upon formation of exiting double stranded RNA.
-<applet load='2HAI_DNA5.pdb' size='400' frame='true' align='left' caption='PDB IDs 2HAI (protein) 1RTD (DNA)' />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).
+<applet load='2HAI_DNA5.pdb' size='400' frame='true' align='left' caption='Figure 2. PDB IDs 2HAI (protein) 1RTD (DNA)' />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. <scene name='NS5B/Ns5b_with_dna/1'>Active site</scene> <scene name='NS5B/Ns5b_with_dna/2'>Beta-hairpin</scene> 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.
-<applet load='2HAI_catalytic3.pdb' size='400' frame='true' align='right' caption='Insert caption here' /> <scene name='NS5B/Ns5b_rna_interactions/1'>NS5B RNA interactions</scene>
+<applet load='2HAI_catalytic3.pdb' size='400' frame='true' align='right' caption='Figure 3.' /> <scene name='NS5B/Ns5b_rna_interactions/1'>NS5B RNA interactions</scene>
 <scene name='NS5B/Native_ns5b/3'>Domains</scene>
@@ Line 22: / Line 22: @@
 [[Image:PolyProtein.jpg]]
-http://www.nature.com/nrmicro/journal/v5/n6/fig_tab/nrmicro1645_F4.html
+Figure 4. http://www.nature.com/nrmicro/journal/v5/n6/fig_tab/nrmicro1645_F4.html
 == '''NS5B + LIGANDS''' ==
-<applet load='2HAI_ligands.pdb' size='400' frame='true' align='right' caption='NS5B' />
+<applet load='2HAI_ligands.pdb' size='400' frame='true' align='right' caption='Figure 5. NS5B in complex with ligands from deposited structures all superimposed on the 1.58Å resolution 2HAI. Ligands are from  ' />
 <scene name='NS5B/Ns5b_with_ligands/3'>Domains</scene>
 <scene name='NS5B/Ns5b_with_ligands/4'>Active site ligands</scene>
 <scene name='NS5B/Ns5b_with_ligands/5'>Allosteric site ligands</scene>

NS5B

From Proteopedia

Revision as of 00:07, 21 April 2009

RNA Dependent RNA Polymerase from Hepatitis C Virus

NS5B + LIGANDS

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