Premium
Dissect Conformational Distribution and Drug‐Induced Population Shift of Prokaryotic rRNA A‐Site
Author(s) -
Qi Xin,
Lu Jia,
Zhao Liang,
Xia Amy,
Xia Tianbing
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.777.1
Subject(s) - binding site , biophysics , population , rna , chemistry , computational biology , drug , biology , biochemistry , medicine , pharmacology , environmental health , gene
Accurate decoding at the ribosomal RNA A‐site is essential in protein synthesis. Previous studies showed that the dynamic behavior of the A‐site would play an important role in the recognition and function of the element. In this study, we aim to understand the mechanism of molecular recognition of prokaryotic A‐site by aminoglycosides. We have employed time‐resolved fluorescence spectroscopy to investigate the complex nature of the conformational equilibrium of the A‐site, and the effects of drug binding. The time‐resolve dynamics probing revealed that in the drug‐free state, the A‐site samples at least four distinct conformations. Changes in the fluorescence decay profiles induced by drug binding showed that population distribution shifts in a drug‐specific manner. Furthermore, time‐resolved anisotropy measurements indicated that motions of A‐site on nanosecond and picosecond timescales are differentially affected by the drug binding. Taken together, these results underscore the importance of understanding the detailed dynamic picture of molecular recognition and can potentially facilitate development of anti‐microbial drugs targeting such dynamic RNA elements. This work was supported in part by funding from UF and a grant from the Robert A. Welch Foundation (AT‐1645).