Two-dimensional combinatorial screening of a bacterial rRNA A-site-like motif library: defining privileged asymmetric internal loops that bind aminoglycosides.

Biochemistry
Tuan Tran, Matthew D Disney

Abstract

RNAs have diverse structures that are important for biological function. These structures include bulges and internal loops that can form tertiary contacts or serve as ligand binding sites. The most commonly exploited RNA drug target for small molecule intervention is the bacterial ribosome, more specifically the rRNA aminoacyl-tRNA site (rRNA A-site) which is a major target for the aminoglycoside class of antibiotics. The bacterial A-site is composed of a 1 x 1 nucleotide all-U internal loop and a 2 x 1 nucleotide all-A internal loop separated by a single GC base pair. Therefore, we probed the molecular recognition of a small library of four aminoglycosides for binding a 16384-member bacterial rRNA A-site-like internal loop library using two-dimensional combinatorial screening (2DCS). 2DCS is a microarray-based method that probes RNA and chemical spaces simultaneously. These studies sought to determine if aminoglycosides select their therapeutic target if given a choice of binding all possible internal loops derived from an A-site-like library. Results show that the bacterial rRNA A-site was not selected by any aminoglycoside. Analyses of selected sequences using the RNA Privileged Space Predictor (RNA-PSP) program show that e...Continue Reading

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Citations

Sep 6, 2012·ACS Chemical Biology·Matthew D DisneyJessica L Childs-Disney
May 25, 2011·Journal of the American Chemical Society·Sai Pradeep VelagapudiMatthew D Disney
Jul 24, 2010·Chemical Communications : Chem Comm·Maria DucaRachid Benhida
Mar 2, 2016·BMC Bioinformatics·Biao LiuMatthew D Disney
Jan 17, 2014·Chemistry : a European Journal·Jean-Patrick JolyRachid Benhida
Dec 23, 2016·Journal of the American Chemical Society·Christopher S EubanksAmanda E Hargrove
Jan 6, 2017·Chemical Communications : Chem Comm·Hélène GuyonLaurent Micouin
Jul 30, 2014·MedChemComm·Marina Y FossoSylvie Garneau-Tsodikova
Dec 5, 2020·Current Protocols in Chemical Biology·Deondre JordanJohn S Schneekloth
Dec 22, 2011·ACS Chemical Biology·Lirui Guan, Matthew D Disney
May 14, 2014·Journal of the American Chemical Society·Joanna Sztuba-SolinskaJohn S Schneekloth
Dec 5, 2018·Biochemistry·Christopher S Eubanks, Amanda E Hargrove

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