Identification of new ClpC1-NTD binders for Mycobacterium tuberculosis drug development

Identification of new ClpC1-NTD binders for Mycobacterium tuberculosis drug development

Abstract MtbClpC1 is a promising drug target against tuberculosis. Recent studies have shown that several natural product antibiotics targeting the unfoldase N-terminal domain can impair MtbClpC1 function resulting in cell death. While the pharmacological properties of these natural product antibiot...

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Bibliographic Details
Main Authors: Katharina Weinhäupl, Louis Meuret, Sandy Desrat, Fanny Roussy, Nelly Morellet, Sandra Beaupierre, Catherine Guillou, Carine van Heijenoort, Olga Abian, Sonia Vega, Ian Wolf, Tatos Akopian, Olga Krandor, Eric Rubin, Adrian Velazquez-Campoy, Diego Gauto, Hugo Fraga
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
Subjects:
Chaperone
Tuberculosis
In silico
Protags
ClpC1
Online Access:https://doi.org/10.1038/s41598-025-87535-1
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Summary:Abstract MtbClpC1 is a promising drug target against tuberculosis. Recent studies have shown that several natural product antibiotics targeting the unfoldase N-terminal domain can impair MtbClpC1 function resulting in cell death. While the pharmacological properties of these natural product antibiotics prevent their use in the clinic, similar molecules binding to the same binding pockets can result in new drugs against Mtb. Here we demonstrate that we successfully used in silico screening to identify new ClpC1 N-terminal domain binders with micromolar affinity from a small compound library. In addition, we experimentally demonstrate that the new compounds bind to the same pockets used by the natural product antibiotics and inhibit ClpC1 function.
ISSN:2045-2322

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