Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding
| Autor: | Paul R. Caron, James P. Griffith, John A. Thomson, Morgenstern Kurt A, Joseph L. Kim, Maureen D. Dwyer, Murcko Mark A, Chao Lin |
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| Rok vydání: | 1998 |
| Předmět: |
Models
Molecular Protein Folding Protein Conformation Molecular Sequence Data mechanism DNA Single-Stranded Hepacivirus Viral Nonstructural Proteins Biology Crystallography X-Ray Protein Structure Secondary Viral Proteins chemistry.chemical_compound Structural Biology Amino Acid Sequence Binding site Molecular Biology Conserved Sequence Nucleoside-triphosphatase Genetics NS3 Oligonucleotide RNA-Binding Proteins Helicase RNA RNA Helicase A helicase Biochemistry chemistry biology.protein Nucleic Acid Conformation X-ray structure hepatitis C Sequence Alignment DNA |
| Zdroj: | Structure. 6:89-100 |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/s0969-2126(98)00010-0 |
| Popis: | Background: Hepatitis C virus (HCV) represents a major health concern as it is responsible for a significant number of hepatitis cases worldwide. Much research has focused on the replicative enzymes of HCV as possible targets for more effective therapeutic agents. HCV NS3 helicase may provide one such suitable target. Helicases are enzymes which can unwind double-stranded regions of DNA or RNA in an ATP-dependent reaction. The structures of several helicases have been published but the structural details as to how ATP binding and hydrolysis are coupled to DNA unwinding are unknown. Results: The structure of the HCV NS3 RNA helicase domain complexed with a single-stranded DNA oligonucleotide has been solved to 2.2 a resolution. The protein consists of three structural domains with the oligonucleotide lying in a groove between the first two domains and the third. The first two domains have an adenylate kinase like fold, including a phosphate-binding loop in the first domain. Conclusions: HCV NS3 helicase is a member of a superfamily of helicases, termed superfamily II. Residues of NS3 helicase which are conserved among superfamily II helicases line an interdomain cleft between the first two domains. The oligonucleotide binds in an orthogonal binding site and contacts relatively few conserved residues. There are no strong sequence-specific interactions with the oligonucleotide bases. |
| Databáze: | OpenAIRE |
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