1GX5

Hepatitis C Virus RNA Polymerase in Complex with GTP and Manganese

Summary for 1GX5

• Entry DOI: 10.2210/pdb1gx5/pdb
• Related: 1C2P 1CSJ 1CU1 1NS3 1QUV 8OHM
• Descriptor: RNA-DIRECTED RNA POLYMERASE, GUANOSINE-5'-TRIPHOSPHATE, MANGANESE (II) ION, ... (4 entities in total)
• Functional Keywords: transferase, polyprotein, glycoprotein, rna-directed rna polymerase, core protein, coat protein, envelope protein, helicase, atp binding, transmembrane, nonstructural protein
• Biological source: HEPATITIS C VIRUS (ISOLATE BK) (HCV)
• Cellular location: Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein. Core protein p19: Virion . Envelope glycoprotein E1: Virion membrane ; Single-pass type I membrane protein . Envelope glycoprotein E2: Virion membrane ; Single-pass type I membrane protein . p7: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Protease NS2-3: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Serine protease NS3: Host endoplasmic reticulum membrane ; Peripheral membrane protein . Non-structural protein 4A: Host endoplasmic reticulum membrane ; Single-pass type I membrane protein . Non-structural protein 4B: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Non-structural protein 5A: Host endoplasmic reticulum membrane ; Peripheral membrane protein . RNA-directed RNA polymerase: Host endoplasmic reticulum membrane ; Single-pass type I membrane protein : P26663
• Total number of polymer chains: 1
• Total formula weight: 61415.43

Authors

Bressanelli, S.,Rey, F.A. (deposition date: 2002-03-27, release date: 2002-04-09, Last modification date: 2024-10-16)

Primary citation

Bressanelli, S.,Tomei, L.,Rey, F.A.,De Francesco, R.
A Structural Analysis of the Hepatitis C Virus RNA Polymerase in Complex with Ribonucleotides
J.Virol., 76:3482-, 2002

PubMed Abstract: 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.

PubMed: 11884572
DOI: 10.1128/JVI.76.7.3482-3492.2002

Experimental method

X-RAY DIFFRACTION (1.7 Å)