Structure, function and cellular dynamics of macromolecular metabolic machines. All living things require purine nucleotides; they serve crucial roles in DNA and RNA, act as neurotransmitters and are involved in the storage and transfer of energy. The proteins responsible for the de novo biosynthesis of purines were recently discovered to associate into a dynamic multi-protein mesoscale assembly called the purinosome. This molecular super-structure enables the cell to have both temporal and spatial control over metabolic flux. The super-resolution image above illustrates how the purinosomes (in magenta) associate with mitochondria (green). Our group is investigating the structural determinants and mechanistic underpinnings of this critical metabolic machine. This work is expected to provide new targets for the development of novel anti-cancer treatments.
Iva Chitrakar, Deborah M. Kim-Holzapfel, Weijie Zhou, and Jarrod B. French (2017) Higher Order Structures in Purine and Pyrimidine Metabolism. J. Struct. Biol. 197(3): 354-364.
French et al. Science (2016) 351:733; Zhao et al. Chem. Comm. (2013) 49:4444; French et al. PNAS (2013) 110:2528.