The Genomic Hdv Ribozyme Utilizes a Previously Unnoticed U-turn Motif to Accomplish Fast Site-specific Catalysis.
From: Department of Chemistry, Single Molecule Analysis Group, University of Michigan, Ann Arbor, MI 48109-1055, USA.
Nucleic acids research
- Publish Date: 2007
- ISSN: 1362-4962
- Volume: 35
- Issue: 6
- Pages: 1933-46
- Medium: Internet
- Language: English
- Citation (JAMA): Sefcikova Jana, Krasovska Maryna V, Sponer Jirí, et al. The Genomic Hdv Ribozyme Utilizes a Previously Unnoticed U-turn Motif to Accomplish Fast Site-specific Catalysis.. Nucleic Acids Res. 2007;35:1933-46
Abstract
The genome of the human hepatitis delta virus (HDV) harbors a self-cleaving catalytic RNA motif, the genomic HDV ribozyme, whose crystal structure shows the dangling nucleotides 5’ of the cleavage site projecting away from the catalytic core. This 5’-sequence contains a clinically conserved U-1 that we find to be essential for fast cleavage, as the order of activity follows U-1 > C-1 > A-1 > G-1, with a >25-fold activity loss from U-1 to G-1. Terbium(III) footprinting detects conformations for the P1.1 stem, the cleavage site wobble pair and the A-minor motif of the catalytic trefoil turn that depend on the identity of the N-1 base. The most tightly folded catalytic core, resembling that of the reaction product, is found in the U-1 wild-type precursor. Molecular dynamics simulations demonstrate that a U-1 forms the most robust kink around the scissile phosphate, exposing it to the catalytic C75 in a previously unnoticed U-turn motif found also, for example, in the hammerhead ribozyme and tRNAs. Strikingly, we find that the common structural U-turn motif serves distinct functions in the HDV and hammerhead ribozymes.
Mesh Headings (Keywords): Base Sequence, Binding Sites, Catalysis, Computer Simulation, Genome, Viral, Hepatitis Delta Virus, Hydrogen Bonding, Magnesium, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Purines, Pyrimidines, RNA, Catalytic, RNA, Viral, Terbium, Uracil
Check for Full Text / PubMed Unique Identifier (PMID): 17337436
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