Inteins as targets for potential antimycobacterial drugs

被引:32
作者
Paulus, H
机构
[1] Boston Biomed Res Inst, Watertown, MA 02472 USA
[2] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
关键词
inteins; mycobacterium tuberculosis; antimycobacterial drugs; protein splicing; RecA; DnaB; thymidylate synthase; DNA gyrase; CcdB toxin; green fluorescent protein; drug screening; drug targets; high throughput screening; review;
D O I
10.2741/1195
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein splicing is a self-catalyzed process mediated by inteins. The observation that inteins occur only in microorganisms and that they often interrupt genes that play an essential role in nucleic acid metabolism makes them attractive as potential antibacterial targets. Because mycobacteria are the only intein-containing bacteria associated with human hosts, inteins would represent highly specific antimycobacterial targets. In Mycobacterium tuberculosis, two important proteins of DNA repair and replication, RecA and DnaB, respectively, are interrupted by inteins that must be excised by protein splicing before these proteins can function. This review describes the screening systems for the detection of mutations or inhibitors that interfere with proteins splicing that have been developed and published to date. In three of these experimental system, inteins have been inserted into proteins that are toxic under certain conditions. Protein splicing therefore leads to conditional growth inhibition or cell death and its inhibition can be monitored in terms of bacterial growth. A fourth assay for protein splicing and its inhibition is based on purified proteins and measures the formation of Green Fluorescent Protein or its inhibition. The advantages of inteins as antimycobacterial targets are discussed.
引用
收藏
页码:S1157 / S1165
页数:9
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