NS5B: Difference between revisions

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<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.

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<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>

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[[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''' ==

<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>

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@@ 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>