Get stuck in: Pantothenate synthetase is an attractive target for the development of novel small-molecule drugs against Mycobacterium tuberculosis. Three related sulfamoyl adenylate inhibitors were designed to closely mimic the structure of the reaction intermediate, pantoyl adenylate. The most potent inhibitor exhibited dissociation and inhibition constants of about 100 nM. The structural elucidation of the compounds bound to the enzyme will aid development of subsequent inhibitors.
Ciulli, A., Scott, D. E., Ando, M., Reyes, F., Saldanha, S. A., Tuck, K. L., Chirgadze, D. Y., Blundell, T. L., & Abell, C. (2008). Inhibition of Mycobacterium tuberculosis pantothenate synthetase by analogues of the reaction intermediate. ChemBioChem, 9(16), 2606-2611. https://doi.org/10.1002/cbic.200800437