title: Structure of the HCV Internal Ribosome Entry Site Subdomain IIa RNA in Complex with a Viral Translation Inhibitor.
abstract: The internal ribosome entry site (IRES) in the 5' untranslated region (UTR) of the hepatitis C virus (HCV) RNA genome is responsible for initiation of viral protein synthesis. The IRES RNA contains autonomously folding domains that are potential targets for antiviral translation inhibitors. Here, we describe the experimental crystal structure determination of the IRES subdomain IIa in complex with a previously discovered benzimidazole translation inhibitor. The structure of an inhibitor complex of the highly conserved IRES subdomain IIa holds promise for structure-based design of new anti-HCV drugs.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Dibrov
authors.forename: Thomas
authors.initials: T
authors.lastname: Hermann
mesh_terms: D020121:5' Untranslated Regions; D000998:Antiviral Agents / Q000737:chemistry; D001483:Base Sequence; D001562:Benzimidazoles / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D016679:Genome, Viral; D016174:Hepacivirus / Q000737:chemistry* / Q000235:genetics; D000067556:Internal Ribosome Entry Sites; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry; D014176:Protein Biosynthesis / Q000187:drug effects; D017434:Protein Structure, Tertiary; D011500:Protein Synthesis Inhibitors / Q000737:chemistry; D012367:RNA, Viral / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D000998:Antiviral Agents; D001562:Benzimidazoles; D000067556:Internal Ribosome Entry Sites; D009841:Oligonucleotides; D011500:Protein Synthesis Inhibitors; D012367:RNA, Viral