Target intelligence / Profile preview

Mycobacterium tuberculosis RecA intein (Mtb RecA intein) (Mtb RecA intein)

Target
Mtb RecA intein
Molecular classification
Enzyme, Autoprocessing protein
01

Overview

The RecA intein is a self-splicing protein element embedded within the RecA protein of Mycobacterium tuberculosis, the pathogen responsible for tuberculosis (Nature Communications, 2015). It acts as an intervening sequence that must be post-translationally removed through a process called protein splicing to generate a functional RecA enzyme (PNAS, 2015). RecA itself is a critical component of the bacterial DNA repair machinery and the SOS response, allowing the pathogen to survive DNA damage and oxidative stress within the host (UniProt, P9WGI7). Because inteins are not found in human proteins, the RecA intein represents a highly selective target for antimicrobial intervention (Journal of Biological Chemistry, 2016). Inhibition of this splicing process by small molecules or metal complexes prevents the maturation of RecA, thereby sensitizing the bacteria to existing antibiotics and host immune defenses (Applied Microbiology and Biotechnology, 2018). Compounds such as cisplatin and certain nucleoside analogs have been shown to effectively block the splicing mechanism, highlighting the potential for this target in treating multi-drug resistant tuberculosis (Angewandte Chemie, 2011).

Other names
RecA intervening sequenceMtb RecA self-splicing elementRecA protein intervening sequence
02

Mechanism of action

Inhibition of the protein splicing mechanism of the RecA intein, which prevents the maturation of the RecA protein and disrupts DNA repair pathways in Mycobacterium tuberculosis (Nature Communications, 2015; Angewandte Chemie, 2011).

03

Biological functions

Protein splicingDNA repairDNA recombination
04

Disease associations

InfectionTuberculosis
05

Safety considerations

Systemic toxicity of platinum-based inhibitorsOff-target effects in human cellsPotential for drug resistance development
06

Interacting drugs

Cisplatin

4 more in the full profile.

07

Biomarkers

RecA protein levelsBacterial DNA damage markersSplicing precursor accumulation

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