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PDBsum entry 1gx5
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Contents |
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* Residue conservation analysis
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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 analysis of the hepatitis c virus RNA polymerase in complex with ribonucleotides.
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Authors
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S.Bressanelli,
L.Tomei,
F.A.Rey,
R.De francesco.
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Ref.
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J Virol, 2002,
76,
3482-3492.
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PubMed id
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Abstract
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We report here the results of a systematic high-resolution X-ray
crystallographic analysis of complexes of the hepatitis C virus (HCV) RNA
polymerase with ribonucleoside triphosphates (rNTPs) and divalent metal ions. An
unexpected observation revealed by this study is the existence of a specific
rGTP binding site in a shallow pocket at the molecular surface of the enzyme, 30
A away from the catalytic site. This previously unidentified rGTP pocket, which
lies at the interface between fingers and thumb, may be an allosteric regulatory
site and could play a role in allowing alternative interactions between the two
domains during a possible conformational change of the enzyme required for
efficient initiation. The electron density map at 1.7-A resolution clearly shows
the mode of binding of the guanosine moiety to the enzyme. In the catalytic
site, density corresponding to the triphosphates of nucleotides bound to the
catalytic metals was apparent in each complex with nucleotides. Moreover, a
network of triphosphate densities was detected; these densities superpose to the
corresponding moieties of the nucleotides observed in the initiation complex
reported for the polymerase of bacteriophage phi6, strengthening the proposal
that the two enzymes initiate replication de novo by similar mechanisms. No
equivalent of the protein stacking platform observed for the priming nucleotide
in the phi6 enzyme is present in HCV polymerase, however, again suggesting that
a change in conformation of the thumb domain takes place upon template binding
to allow for efficient de novo initiation of RNA synthesis.
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