Riboswitches as antibacterial drug targets

被引：0
作者：
Kenneth F Blount
Ronald R Breaker
机构：
[1] Cellular and Developmental Biology,Department of Molecular
[2] Yale University,Department of Molecular Biophysics and Biochemistry
[3] Yale University,undefined
[4] Howard Hughes Medical Institute,undefined
[5] Yale University,undefined
来源：
Nature Biotechnology | 2006年 / 24卷
关键词：
D O I：
暂无
中图分类号：
学科分类号：
摘要：
New validated cellular targets are needed to reinvigorate antibacterial drug discovery. This need could potentially be filled by riboswitches—messenger RNA (mRNA) structures that regulate gene expression in bacteria. Riboswitches are unique among RNAs that serve as drug targets in that they have evolved to form structured and highly selective receptors for small drug-like metabolites. In most cases, metabolite binding to the receptor represses the expression of the gene(s) encoded by the mRNA. If a new metabolite analog were designed that binds to the receptor, the gene(s) regulated by that riboswitch could be repressed, with a potentially lethal effect to the bacteria. Recent work suggests that certain antibacterial compounds discovered decades ago function at least in part by targeting riboswitches. Herein we will summarize the experiments validating riboswitches as drug targets, describe the existing technology for riboswitch drug discovery and discuss the challenges that may face riboswitch drug discoverers.
引用
收藏
页码：1558 / 1564
页数：6
相关论文
共 188 条
[51]  
Matassova NB(2000): potential for Annu. Rev. Nutr. 20 153-167
[52]  
Murchie AI(2005) production of vitamin-enriched foods Mol. Cell 18 49-60
[53]  
Steitz TA(2005)Genetic mapping of regulatory mutations of Biochemistry 44 13404-13414
[54]  
Hermann T(1958) riboflavin operon Biochim. Biophys. Acta 29 333-344
[55]  
Tor Y(1986)Riboflavin operon of Physiol. Chem. Phys. Med. NMR 18 159-164
[56]  
Mandal M(1987): unusual symmetric arrangement of the regulatory region J. Bacteriol. 169 2977-2983
[57]  
Boese B(2005)Crystal structures of the thi-box riboswitch bound to thiamine pyrophosphate analogs reveal adaptive RNA-small molecule recognition Bioorg. Chem. 33 338-344
[58]  
Barrick JE(2006)Control of gene expression by a natural metabolite-responsive ribozyme J. Bacteriol. 188 3674-3681
[59]  
Winkler WC(2004)High-throughput-compatible assay for Proc. Natl. Acad. Sci. USA 101 6421-6426
[60]  
Breaker RR(2005) riboswitch metabolite dependence Genome Biol. 6 R70.1-R70.10
12345678910