Focused Overview of Mycobacterium tuberculosis VapBC Toxin–Antitoxin Systems Regarding Their Structural and Functional Aspects: Including Insights on Biomimetic Peptides

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis, is a lethal infectious disease of significant public health concern. The rise of multidrug-resistant and drug-tolerant strains has necessitated novel approaches to combat the disease. Toxin–antitoxin (TA) systems, key players in bacterial adaptive responses, are prevalent in prokaryotic genomes and have been linked to tuberculosis. The genome of M. tuberculosis strains harbors an unusually high number of TA systems, prompting questions about their biological roles. The VapBC family, a representative type II TA system, is characterized by the VapC toxin, featuring a PilT N-terminal domain with nuclease activity. Its counterpart, VapB, functions as an antitoxin, inhibiting VapC’s activity. Additionally, we explore peptide mimics designed to replicate protein helical structures in this review. Investigating these synthetic peptides offers fresh insights into molecular interactions, potentially leading to therapeutic applications. These synthetic peptides show promise as versatile tools for modulating cellular processes and protein–protein interactions. We examine the rational design strategies employed to mimic helical motifs, their biophysical properties, and potential applications in drug development and bioengineering. This review aims to provide an in-depth understanding of TA systems by introducing known complex structures, with a focus on both structural aspects and functional and molecular details associated with each system.

Discovery of Antimicrobial Agents Based on Structural and Functional Study of the Klebsiella pneumoniae MazEF Toxin–Antitoxin System

“…In type II TA systems, antitoxin is a small protein. This protein antitoxin acts as an inhibitor binding to protein toxin by forming protein complex [15,16]. In type III TA systems, antitoxins take the form of RNA and form an RNA-protein complex with its coupled toxin protein [17].…”