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PDBsum entry 3bsn
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Transferase/RNA
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PDB id
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3bsn
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References listed in PDB file
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Key reference
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Title
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Structural insights into mechanisms of catalysis and inhibition in norwalk virus polymerase.
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Authors
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D.F.Zamyatkin,
F.Parra,
J.M.Alonso,
D.A.Harki,
B.R.Peterson,
P.Grochulski,
K.K.Ng.
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Ref.
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J Biol Chem, 2008,
283,
7705-7712.
[DOI no: ]
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PubMed id
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Abstract
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Crystal structures of Norwalk virus polymerase bound to an RNA primer-template
duplex and either the natural substrate CTP or the inhibitor 5-nitrocytidine
triphosphate have been determined to 1.8A resolution. These structures reveal a
closed conformation of the polymerase that differs significantly from previously
determined open structures of calicivirus and picornavirus polymerases. These
closed complexes are trapped immediately prior to the nucleotidyl transfer
reaction, with the triphosphate group of the nucleotide bound to two manganese
ions at the active site, poised for reaction to the 3'-hydroxyl group of the RNA
primer. The positioning of the 5-nitrocytidine triphosphate nitro group between
the alpha-phosphate and the 3'-hydroxyl group of the primer suggests a novel,
general approach for the design of antiviral compounds mimicking natural
nucleosides and nucleotides.
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Figure 2.
FIGURE 2. Stereoscopic overall views of (A, top; C, side)
NV RdRP·RNA·Mn^2+·NCT complex and (B, top;
D, side) uncomplexed NV RdRP (Protein Data Bank code 1SH0 (11)).
The primer (yellow) and template (magenta) strands of RNA, NCT
(red), and Mn^2+ (pink) are drawn. The C-terminal tail of
unbound NV RdRP is highlighted in red. The largest
conformational changes in the thumb and fingers domains
following the binding of RNA are highlighted with arrows.
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Figure 3.
FIGURE 3. Stereoscopic views of the active site of the NCT
(A and C) and CTP (B and D) complexes. In panels A and B,
coordination bonds (red dashes) with Mn^2+ ions A and B (pink
spheres), and hydrogen bonds (red dashes) between the bound
nucleotide (magenta), key water molecules (red spheres), and the
protein are drawn. In panels C and D, Arg-182, the bound
nucleotide, Mn^2+ ions, and the terminal nucleotide of the
primer were removed prior to 20 rounds of refinement and (|F[o]|
- |F[c]|) electron density map calculation (3  contour). Figs. 2 and 3
were prepared using PyMOL (38).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2008,
283,
7705-7712)
copyright 2008.
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