Nature Communications (Jan 2021)
Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site
- 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
Affiliations
- Vitor Mendes
- Department of Biochemistry, University of Cambridge
- Simon R. Green
- Drug Discovery Unit, College of Life Sciences, University of Dundee
- Joanna C. Evans
- MRC/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 Town
- Jeannine Hess
- Department of Chemistry, University of Cambridge
- Michal Blaszczyk
- Department of Biochemistry, University of Cambridge
- Christina Spry
- Department of Chemistry, University of Cambridge
- Owain Bryant
- Department of Biochemistry, University of Cambridge
- James Cory-Wright
- Department of Biochemistry, University of Cambridge
- Daniel S-H. Chan
- Department of Chemistry, University of Cambridge
- Pedro H. M. Torres
- Department of Biochemistry, University of Cambridge
- Zhe Wang
- Division of Infectious Diseases, Weill Department of Medicine, Weill Cornell Medical College
- Navid Nahiyaan
- Division of Infectious Diseases, Weill Department of Medicine, Weill Cornell Medical College
- Sandra O’Neill
- Drug Discovery Unit, College of Life Sciences, University of Dundee
- Sebastian Damerow
- Drug Discovery Unit, College of Life Sciences, University of Dundee
- John Post
- Drug Discovery Unit, College of Life Sciences, University of Dundee
- Tracy Bayliss
- Drug Discovery Unit, College of Life Sciences, University of Dundee
- Sasha L. Lynch
- MRC/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 Town
- Anthony G. Coyne
- Department of Chemistry, University of Cambridge
- Peter C. Ray
- Drug Discovery Unit, College of Life Sciences, University of Dundee
- Chris Abell
- Department of Chemistry, University of Cambridge
- Kyu Y. Rhee
- Division of Infectious Diseases, Weill Department of Medicine, Weill Cornell Medical College
- Helena I. M. Boshoff
- Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health
- Clifton E. Barry
- MRC/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 Town
- Valerie Mizrahi
- MRC/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 Town
- Paul G. Wyatt
- Drug Discovery Unit, College of Life Sciences, University of Dundee
- Tom L. Blundell
- Department of Biochemistry, University of Cambridge
- DOI
- https://doi.org/10.1038/s41467-020-20224-x
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 12
Abstract
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.
