Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site
oleh: 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
| Format: | Article |
|---|---|
| Diterbitkan: | Nature Portfolio 2021-01-01 |
Deskripsi
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.