Bacillus anthracis Inosine 5'-Monophosphate Dehydrogenase in Action: The First Bacterial Series of Structures of Phosphate Ion-, Substrate-, and Product-Bound Complexes

M. Makowska-Grzyska, et al. , 51(31), 6148-6163, Biochemistry, 2012

IMPDH inhibitors have broad clinical applications in cancer treatment, antiviral drug development, and as immuno-supressants. The authors have determined three crystal structures for Bacillus anthracis IMPDH. The newly identified structures include a phosphate ion -bound form (apoenzyme), in complex with its substrate, and in complex with its product. Kinetics of enzymatic reaction of the apoenzyme were also determined, as well as inhibitory effects of two compounds, XMP and MPA. The Octet RED system was utilized to analyze binding of inhibitors to biotinylated IMPDH proteins with Super Streptavidin biosensors.

Read More