AI Article Synopsis
- This study reveals that coumarin-based nitrofuranyl calanolides (NFCs) can interact with the protein Rv2466c, creating a ternary complex that leads to enhanced fluorescence when reduced.
- It was found that a specific fragment of the mycothiol (MSH), known as acetylated cysteine-glucosamine (AcCys-GlcN), effectively binds to Rv2466c and is crucial for the reduction of NFCs.
- The research also suggests that the new fluorescent NFC probe could enable rapid and cost-effective detection of Mycobacterium tuberculosis, aiding in timely drug susceptibility testing for better TB treatment outcomes.
Article Abstract
Firstly, this study demonstrated that natural product-inspired coumarin-based nitrofuranyl calanolides (NFCs) can form the Rv2466c-mycothiol (MSH)-NFC (RvMN) ternary complex via NFC binding to W21, N51, and Y61 of Rv2466c and be specifically reduced by Rv2466c, which is accompanied by the generation of a high level of fluorescence. Additionally, the results unveiled that the acetylated cysteine-glucosamine (AcCys-GlcN) motif of MSH is sufficient to interact with Rv2466c and adopt the active conformation that is essential for fully reducing NFCs. Further clinical translational investigation in this Article indicated that the novel fluorescent NFC probe can serve as a much needed high-throughput and low-cost detection method for detection of living Mycobacterium tuberculosis ( Mtb) and can precisely determine MIC values for a full range of available drugs. This method can greatly facilitate the development of phenotypic drug-susceptibility testing (pDST) that will allow the point-of-care treatment of tuberculosis (TB) within a week after diagnosis.
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| http://dx.doi.org/10.1021/acsinfecdis.9b00006 | DOI Listing |
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