Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site
The bifunctional enzyme CoaBC catalyses the second and third step in the Coenzyme A (CoA) biosynthesis pathway and is of interest as a M. tuberculosis drug target. Here, the authors present the full-length crystal structure of Mycobacterium smegmatis CoaBC, which is regulated by CoA and CoA thioeste...
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Nature Publishing Group
2021-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-020-20224-x |
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doaj-dfbd7ac1fa2f42d49910fcdc7940c42e2021-01-10T12:17:57ZengNature Publishing GroupNature Communications2041-17232021-01-0112111210.1038/s41467-020-20224-xInhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric siteVitor Mendes0Simon R. Green1Joanna C. Evans2Jeannine Hess3Michal Blaszczyk4Christina Spry5Owain Bryant6James Cory-Wright7Daniel S-H. Chan8Pedro H. M. Torres9Zhe Wang10Navid Nahiyaan11Sandra O’Neill12Sebastian Damerow13John Post14Tracy Bayliss15Sasha L. Lynch16Anthony G. Coyne17Peter C. Ray18Chris Abell19Kyu Y. Rhee20Helena I. M. Boshoff21Clifton E. Barry22Valerie Mizrahi23Paul G. Wyatt24Tom L. Blundell25Department of Biochemistry, University of CambridgeDrug Discovery Unit, College of Life Sciences, University of DundeeMRC/NHLS/UCT Molecular Mycobacteriology Research Unit & DST/NRF Centre of Excellence for Biomedical TB Research & Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine and Department of Pathology, Faculty of Health Sciences, University of Cape TownDepartment of Chemistry, University of CambridgeDepartment of Biochemistry, University of CambridgeDepartment of Chemistry, University of CambridgeDepartment of Biochemistry, University of CambridgeDepartment of Biochemistry, University of CambridgeDepartment of Chemistry, University of CambridgeDepartment of Biochemistry, University of CambridgeDivision of Infectious Diseases, Weill Department of Medicine, Weill Cornell Medical CollegeDivision of Infectious Diseases, Weill Department of Medicine, Weill Cornell Medical CollegeDrug Discovery Unit, College of Life Sciences, University of DundeeDrug Discovery Unit, College of Life Sciences, University of DundeeDrug Discovery Unit, College of Life Sciences, University of DundeeDrug Discovery Unit, College of Life Sciences, University of DundeeMRC/NHLS/UCT Molecular Mycobacteriology Research Unit & DST/NRF Centre of Excellence for Biomedical TB Research & Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine and Department of Pathology, Faculty of Health Sciences, University of Cape TownDepartment of Chemistry, University of CambridgeDrug Discovery Unit, College of Life Sciences, University of DundeeDepartment of Chemistry, University of CambridgeDivision of Infectious Diseases, Weill Department of Medicine, Weill Cornell Medical CollegeTuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of HealthMRC/NHLS/UCT Molecular Mycobacteriology Research Unit & DST/NRF Centre of Excellence for Biomedical TB Research & Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine and Department of Pathology, Faculty of Health Sciences, University of Cape TownMRC/NHLS/UCT Molecular Mycobacteriology Research Unit & DST/NRF Centre of Excellence for Biomedical TB Research & Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine and Department of Pathology, Faculty of Health Sciences, University of Cape TownDrug Discovery Unit, College of Life Sciences, University of DundeeDepartment of Biochemistry, University of CambridgeThe bifunctional enzyme CoaBC catalyses the second and third step in the Coenzyme A (CoA) biosynthesis pathway and is of interest as a M. tuberculosis drug target. Here, the authors present the full-length crystal structure of Mycobacterium smegmatis CoaBC, which is regulated by CoA and CoA thioesters and forms a dodecamer and by performing a high-throughput screen they identify selective inhibitors of M. tuberculosis CoaB that bind to an allosteric site within CoaB.https://doi.org/10.1038/s41467-020-20224-x |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Vitor Mendes Simon R. Green Joanna C. Evans Jeannine Hess Michal Blaszczyk Christina Spry Owain Bryant James Cory-Wright Daniel S-H. Chan Pedro H. M. Torres Zhe Wang Navid Nahiyaan Sandra O’Neill Sebastian Damerow John Post Tracy Bayliss Sasha L. Lynch Anthony G. Coyne Peter C. Ray Chris Abell Kyu Y. Rhee Helena I. M. Boshoff Clifton E. Barry Valerie Mizrahi Paul G. Wyatt Tom L. Blundell |
| spellingShingle |
Vitor Mendes Simon R. Green Joanna C. Evans Jeannine Hess Michal Blaszczyk Christina Spry Owain Bryant James Cory-Wright Daniel S-H. Chan Pedro H. M. Torres Zhe Wang Navid Nahiyaan Sandra O’Neill Sebastian Damerow John Post Tracy Bayliss Sasha L. Lynch Anthony G. Coyne Peter C. Ray Chris Abell Kyu Y. Rhee Helena I. M. Boshoff Clifton E. Barry Valerie Mizrahi Paul G. Wyatt Tom L. Blundell Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site Nature Communications |
| author_facet |
Vitor Mendes Simon R. Green Joanna C. Evans Jeannine Hess Michal Blaszczyk Christina Spry Owain Bryant James Cory-Wright Daniel S-H. Chan Pedro H. M. Torres Zhe Wang Navid Nahiyaan Sandra O’Neill Sebastian Damerow John Post Tracy Bayliss Sasha L. Lynch Anthony G. Coyne Peter C. Ray Chris Abell Kyu Y. Rhee Helena I. M. Boshoff Clifton E. Barry Valerie Mizrahi Paul G. Wyatt Tom L. Blundell |
| author_sort |
Vitor Mendes |
| title |
Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site |
| title_short |
Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site |
| title_full |
Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site |
| title_fullStr |
Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site |
| title_full_unstemmed |
Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site |
| title_sort |
inhibiting mycobacterium tuberculosis coabc by targeting an allosteric site |
| publisher |
Nature Publishing Group |
| series |
Nature Communications |
| issn |
2041-1723 |
| publishDate |
2021-01-01 |
| description |
The bifunctional enzyme CoaBC catalyses the second and third step in the Coenzyme A (CoA) biosynthesis pathway and is of interest as a M. tuberculosis drug target. Here, the authors present the full-length crystal structure of Mycobacterium smegmatis CoaBC, which is regulated by CoA and CoA thioesters and forms a dodecamer and by performing a high-throughput screen they identify selective inhibitors of M. tuberculosis CoaB that bind to an allosteric site within CoaB. |
| url |
https://doi.org/10.1038/s41467-020-20224-x |
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