IMR Press / FBL / Volume 8 / Issue 6 / DOI: 10.2741/1195

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Inteins as targets for potential antimycobacterial drugs
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1 Boston Biomedical Research Institute, Watertown, Massachusetts 02472, and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115

Academic Editor: Jens Eckstein

Front. Biosci. (Landmark Ed) 2003, 8(6), 1157–1165;
Published: 1 September 2003
(This article belongs to the Special Issue Current topics in lead discovery)

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.

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