2O3V

Crystal Structure of the Homo sapiens Cytoplasmic Ribosomal Decoding Site complexed with paromamine derivative NB33

Summary for 2O3V

• Entry DOI: 10.2210/pdb2o3v/pdb
• Related: 2FQN 2G5K 2O3W 2O3X 2O3Y
• Descriptor: RNA (5'-R(*UP*UP*GP*CP*GP*UP*CP*GP*CP*UP*CP*CP*GP*GP*AP*AP*AP*AP*GP*UP*CP*GP*C)-3'), (2S,3R,4R,5S,6R)-3-AMINO-4-({[(2S,3R,4R,5S,6R)-3-AMINO-2-{[(1R,2R,3S,4R,6S)-4,6-DIAMINO-2,3-DIHYDROXYCYCLOHEXYL]OXY}-5-HYDROXY-6-(HYDROXYMETHYL)TETRAHYDRO-2H-PYRAN-4-YL]OXY}METHOXY)-6-(HYDROXYMETHYL)TETRAHYDRO-2H-PYRAN-2,5-DIOL (3 entities in total)
• Functional Keywords: aminoglycoside, antibiotics, ribosome, decoding site, homo sapiens, eukaryote, cytoplasmic, translation inhibition, stop codon readthrough, rna
• Total number of polymer chains: 2
• Total formula weight: 15225.34

Authors

Kondo, J.,Hainrichson, M.,Nudelman, I.,Shallom-Shezifi, D.,Baasov, T.,Westhof, E. (deposition date: 2006-12-02, release date: 2007-11-06, Last modification date: 2023-12-27)

Primary citation

Kondo, J.,Hainrichson, M.,Nudelman, I.,Shallom-Shezifi, D.,Barbieri, C.M.,Pilch, D.S.,Westhof, E.,Baasov, T.
Differential Selectivity of Natural and Synthetic Aminoglycosides towards the Eukaryotic and Prokaryotic Decoding A Sites.
Chembiochem, 8:1700-1709, 2007

PubMed Abstract: The lack of absolute prokaryotic selectivity of natural antibiotics is widespread and is a significant clinical problem. The use of this disadvantage of aminoglycoside antibiotics for the possible treatment of human genetic diseases is extremely challenging. Here, we have used a combination of biochemical and structural analysis to compare and contrast the molecular mechanisms of action and the structure-activity relationships of a new synthetic aminoglycoside, NB33, and a structurally similar natural aminoglycoside apramycin. The data presented herein demonstrate the general molecular principles that determine the decreased selectivity of apramycin for the prokaryotic decoding site, and the increased selectivity of NB33 for the eukaryotic decoding site. These results are therefore extremely beneficial for further research on both the design of new aminoglycoside-based antibiotics with diminished deleterious effects on humans, as well as the design of new aminoglycoside-based structures that selectively target the eukaryotic ribosome.

PubMed: 17705310
DOI: 10.1002/cbic.200700271

Experimental method

X-RAY DIFFRACTION (2.8 Å)