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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-87535-1 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Katharina Weinhäupl |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-12aa651f1e354605990a4377bf109206 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-12aa651f1e354605990a4377bf1092062025-02-09T12:34:27ZengNature PortfolioScientific Reports2045-23222025-02-0115111410.1038/s41598-025-87535-1Identification of new ClpC1-NTD binders for Mycobacterium tuberculosis drug developmentKatharina Weinhäupl0Louis Meuret1Sandy Desrat2Fanny Roussy3Nelly Morellet4Sandra Beaupierre5Catherine Guillou6Carine van Heijenoort7Olga Abian8Sonia Vega9Ian Wolf10Tatos Akopian11Olga Krandor12Eric Rubin13Adrian Velazquez-Campoy14Diego Gauto15Hugo Fraga16Institute for Research and Innovation in HealthI3SInstitut de Chimie des Substances Naturelles (ICSN), Centre national de la recherche scientifique (CNRS) Institut de Chimie des Substances Naturelles (ICSN), Centre national de la recherche scientifique (CNRS) Institut de Chimie des Substances Naturelles (ICSN), Centre national de la recherche scientifique (CNRS) Institut de Chimie des Substances Naturelles (ICSN), Centre national de la recherche scientifique (CNRS) Institut de Chimie des Substances Naturelles (ICSN), Centre national de la recherche scientifique (CNRS) Institut de Chimie des Substances Naturelles (ICSN), Centre national de la recherche scientifique (CNRS) Institut de Chimie des Substances Naturelles (ICSN), Centre national de la recherche scientifique (CNRS) Institute for Health Research Aragon (IIS Aragon)Institute of Biocomputation and Physics of Complex Systems (BIFI), University of ZaragozaHarvard School of Public HealthHarvard School of Public HealthHarvard School of Public HealthHarvard School of Public HealthInstitute for Health Research Aragon (IIS Aragon)Institut de Chimie des Substances Naturelles (ICSN), Centre national de la recherche scientifique (CNRS) Institute for Research and Innovation in HealthI3SAbstract 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.https://doi.org/10.1038/s41598-025-87535-1ChaperoneTuberculosisIn silicoProtagsClpC1 |
| spellingShingle | 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 Identification of new ClpC1-NTD binders for Mycobacterium tuberculosis drug development Scientific Reports Chaperone Tuberculosis In silico Protags ClpC1 |
| title | Identification of new ClpC1-NTD binders for Mycobacterium tuberculosis drug development |
| title_full | Identification of new ClpC1-NTD binders for Mycobacterium tuberculosis drug development |
| title_fullStr | Identification of new ClpC1-NTD binders for Mycobacterium tuberculosis drug development |
| title_full_unstemmed | Identification of new ClpC1-NTD binders for Mycobacterium tuberculosis drug development |
| title_short | Identification of new ClpC1-NTD binders for Mycobacterium tuberculosis drug development |
| title_sort | identification of new clpc1 ntd binders for mycobacterium tuberculosis drug development |
| topic | Chaperone Tuberculosis In silico Protags ClpC1 |
| url | https://doi.org/10.1038/s41598-025-87535-1 |
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