1gx6
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HEPATITIS C VIRUS RNA POLYMERASE IN COMPLEX WITH UTP AND MANGANESE
OverviewOverview
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.
About this StructureAbout this Structure
1GX6 is a Single protein structure of sequence from Hepatitis c virus genotype 1b (isolate bk) with MN and UTP as ligands. Active as RNA-directed RNA polymerase, with EC number 2.7.7.48 Structure known Active Site: UT1. Full crystallographic information is available from OCA.
ReferenceReference
Structural analysis of the hepatitis C virus RNA polymerase in complex with ribonucleotides., Bressanelli S, Tomei L, Rey FA, De Francesco R, J Virol. 2002 Apr;76(7):3482-92. PMID:11884572
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- Hepatitis c virus genotype 1b (isolate bk)
- RNA-directed RNA polymerase
- Single protein
- Bressanelli, S.
- Rey, F.A.
- MN
- UTP
- 3d-structure.
- Atp-binding
- Coat protein
- Core protein
- Envelope protein
- Glycoprotein
- Helicase
- Initiation
- Nonstructural protein hydrolase
- Polyprotein
- Rna-dependent rna polymerase
- Rna-directed rna polymerase
- Serine protease
- Transferase
- Transmembrane
- Virus replication