Author:
Wall Diana A.,Tarrant Seanan P.,Wang Chunyu,Mills Kenneth V.,Lennon Christopher W.
Abstract
Protein splicing is a post-translational process by which an intervening polypeptide, or intein, catalyzes its own removal from the flanking polypeptides, or exteins, concomitant with extein ligation. Although inteins are highly abundant in the microbial world, including within several human pathogens, they are absent in the genomes of metazoans. As protein splicing is required to permit function of essential proteins within pathogens, inteins represent attractive antimicrobial targets. Here we review key proteins interrupted by inteins in pathogenic mycobacteria and fungi, exciting discoveries that provide proof of concept that intein activity can be inhibited and that this inhibition has an effect on the host organism’s fitness, and bioanalytical methods that have been used to screen for intein activity. We also consider potential off-target inhibition of hedgehog signaling, given the similarity in structure and function of inteins and hedgehog autoprocessing domains.
Subject
Biochemistry, Genetics and Molecular Biology (miscellaneous),Molecular Biology,Biochemistry
Reference106 articles.
1. Development of a Positive Genetic Selection System for Inhibition of Protein Splicing Using Mycobacterial Inteins in Escherichia coli DNA Gyrase Subunit A;Adam;J. Mol. Microbiol. Biotechnol.,2002
2. Nature’s Recipe for Splitting Inteins;Aranko;Protein Eng. Des. Selection,2014
3. Mobile Self-Splicing Introns and Inteins as Environmental Sensors;Belfort;Curr. Opin. Microbiol.,2017
4. Cell Killing by the F Plasmid CcdB Protein Involves Poisoning of DNA-Topoisomerase II Complexes;Bernard;J. Mol. Biol.,1992
5. Off‐Pathway‐Sensitive Protein‐Splicing Screening Based on a Toxin/Antitoxin System;Beyer;Chembiochem,2019
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