2OE5

1.5 A X-ray crystal structure of Apramycin complex with RNA fragment GGCGUCGCUAGUACCG/GGUACUAAAAGUCGCCC containing the human ribosomal decoding A site: RNA construct with 3'-overhang

Summary for 2OE5

• Entry DOI: 10.2210/pdb2oe5/pdb
• Related: 2OE6 2OE8
• Descriptor: RNA (5'-R(*GP*GP*CP*GP*UP*CP*GP*CP*UP*AP*GP*UP*AP*CP*CP*G)-3'), RNA (5'-R(*GP*GP*UP*AP*CP*UP*AP*AP*AP*AP*GP*UP*CP*GP*CP*CP*C)-3'), SULFATE ION, ... (6 entities in total)
• Functional Keywords: aminoglycoside antibiotics, apramycin, ribosomal decoding site, a site, homo sapiens, rna duplex, rna
• Total number of polymer chains: 2
• Total formula weight: 11239.65

Authors

Hermann, T.,Tereshko, V.,Skripkin, E.,Patel, D.J. (deposition date: 2006-12-28, release date: 2007-02-13, Last modification date: 2024-04-03)

Primary citation

Hermann, T.,Tereshko, V.,Skripkin, E.,Patel, D.J.
Apramycin recognition by the human ribosomal decoding site.
Blood Cells Mol.Dis., 38:193-198, 2007

PubMed Abstract: Aminoglycoside antibiotics bind specifically to the bacterial ribosomal decoding-site RNA and thereby interfere with fidelity but not efficiency of translation. Apramycin stands out among aminoglycosides for its mechanism of action which is based on blocking translocation and its ability to bind also to the eukaryotic decoding site despite differences in key residues required for apramycin recognition by the bacterial target. To elucidate molecular recognition of the eukaryotic decoding site by apramycin we have determined the crystal structure of an oligoribonucleotide containing the human sequence free and in complex with the antibiotic at 1.5 A resolution. The drug binds in the deep groove of the RNA which forms a continuously stacked helix comprising non-canonical C.A and G.A base pairs and a bulged-out adenine. The binding mode of apramycin at the human decoding-site RNA is distinct from aminoglycoside recognition of the bacterial target, suggesting a molecular basis for the actions of apramycin in eukaryotes and bacteria.

PubMed: 17258916
DOI: 10.1016/j.bcmd.2006.11.006

Experimental method

X-RAY DIFFRACTION (1.51 Å)