期刊
NUCLEIC ACIDS RESEARCH
卷 40, 期 7, 页码 3042-3055出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkr1152
关键词
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资金
- German Research Council [DFG Pe494/1-1, DFG Pe494/1-2, DFG ME1830, DFG Pe494/8-1]
- European Social Funds
- state of Schleswig-Holstein within a competence center [ASH2000/32/19535]
- EU [WP3]
- Institute of Molecular Medicine
- Deutsche Forschungsgemeinschaft
Oligonucleotides as short as 6 nt in length have been shown to bind specifically and tightly to proteins and affect their biological function. Yet, sparse structural data are available for corresponding complexes. Employing a recently developed hexanucleotide array, we identified hexadeoxyribonucleotides that bind specifically to the 3C protease of hepatitis A virus (HAV 3C(pro)). Inhibition assays in vitro identified the hexanucleotide 5'-GGGGGT-3' (G(5)T) as a 3C(pro) protease inhibitor. Using H-1 NMR spectroscopy, G(5)T was found to form a G-quadruplex, which might be considered as a minimal aptamer. With the help of H-1, N-15-HSQC experiments the binding site for G(5)T was located to the C-terminal beta-barrel of HAV 3C(pro). Importantly, the highly conserved KFRDI motif, which has previously been identified as putative viral RNA binding site, is not part of the G(5)T-binding site, nor does G(5)T interfere with the binding of viral RNA. Our findings demonstrate that sequence-specific nucleic acid-protein interactions occur with oligonucleotides as small as hexanucleotides and suggest that these compounds may be of pharmaceutical relevance.
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