6TGV
Crystal structure of Mycobacterium smegmatis CoaBC in complex with CTP and FMN
Summary for 6TGV
| Entry DOI | 10.2210/pdb6tgv/pdb |
| Descriptor | Coenzyme A biosynthesis bifunctional protein CoaBC, CYTIDINE-5'-TRIPHOSPHATE, 1,2-ETHANEDIOL, ... (6 entities in total) |
| Functional Keywords | coabc, bifunctional phosphopantothenoylcysteine decarboxylase/phosphopantothenate-cysteine ligase, phosphopantothenate-cysteine ligase, phosphopantothenoylcysteine decarboxylase, phosphopantothenoylcysteine synthetase, ligase |
| Biological source | Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium smegmatis) |
| Total number of polymer chains | 4 |
| Total formula weight | 177389.72 |
| Authors | Mendes, V.,Blaszczyk, M.,Bryant, O.,Cory-Wright, J.,Blundell, T.L. (deposition date: 2019-11-18, release date: 2020-11-25, Last modification date: 2024-05-15) |
| Primary citation | Mendes, V.,Green, S.R.,Evans, J.C.,Hess, J.,Blaszczyk, M.,Spry, C.,Bryant, O.,Cory-Wright, J.,Chan, D.S.,Torres, P.H.M.,Wang, Z.,Nahiyaan, N.,O'Neill, S.,Damerow, S.,Post, J.,Bayliss, T.,Lynch, S.L.,Coyne, A.G.,Ray, P.C.,Abell, C.,Rhee, K.Y.,Boshoff, H.I.M.,Barry, C.E.,Mizrahi, V.,Wyatt, P.G.,Blundell, T.L. Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site. Nat Commun, 12:143-143, 2021 Cited by PubMed Abstract: Coenzyme A (CoA) is a fundamental co-factor for all life, involved in numerous metabolic pathways and cellular processes, and its biosynthetic pathway has raised substantial interest as a drug target against multiple pathogens including Mycobacterium tuberculosis. The biosynthesis of CoA is performed in five steps, with the second and third steps being catalysed in the vast majority of prokaryotes, including M. tuberculosis, by a single bifunctional protein, CoaBC. Depletion of CoaBC was found to be bactericidal in M. tuberculosis. Here we report the first structure of a full-length CoaBC, from the model organism Mycobacterium smegmatis, describe how it is organised as a dodecamer and regulated by CoA thioesters. A high-throughput biochemical screen focusing on CoaB identified two inhibitors with different chemical scaffolds. Hit expansion led to the discovery of potent and selective inhibitors of M. tuberculosis CoaB, which we show to bind to a cryptic allosteric site within CoaB. PubMed: 33420031DOI: 10.1038/s41467-020-20224-x PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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