2o3w
From Proteopedia
Crystal Structure of the Homo sapiens Cytoplasmic Ribosomal Decoding Site in presence of paromomycin
Overview
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.
About this Structure
2O3W is a Single protein structure. Full crystallographic information is available from OCA.
Reference
Differential selectivity of natural and synthetic aminoglycosides towards the eukaryotic and prokaryotic decoding A sites., Kondo J, Hainrichson M, Nudelman I, Shallom-Shezifi D, Barbieri CM, Pilch DS, Westhof E, Baasov T, Chembiochem. 2007 Sep 24;8(14):1700-9. PMID:17705310 Page seeded by OCA on Sun May 4 10:17:53 2008
