Structure of Cryptosporidium IMP de­hydrogenase bound to an inhibitor with in vivo antiparasitic activity


Inosine 50-monophosphate dehydrogenase (IMPDH) is a promising target for the treatment of Cryptosporidium infections. Here, the structure of C. parvum IMPDH (CpIMPDH) in complex with inosine 50-monophosphate (IMP) and P131, an inhibitor with in vivo anticryptosporidial activity, is reported. P131 contains two aromatic groups, one of which interacts with the hypoxanthine ring of IMP, while the second interacts with the aromatic ring of a tyrosine in the adjacent subunit. In addition, the amine and NO2 moieties bind in hydrated cavities, forming water-mediated hydrogen bonds to the protein. The design of compounds to replace these water molecules is a new strategy for the further optimization of C. parvum inhibitors for both antiparasitic and antibacterial applications.



Cryptosporidium, inosine 5'-monophosphate dehydrogenase, P131


Copyright 2015 Acta Crystallographica. Recommended citation: Kim, Youngchang, Magdalena Makowska-Grzyska, Suresh Kumar Gorla, Deviprasad R. Gollapalli, Gregory D. Cuny, Andrzej Joachimiak, and Lizbeth Hedstrom. "Structure of Cryptosporidium IMP dehydrogenase bound to an inhibitor with in vivo antiparasitic activity." Acta Crystallographica Section F: Structural Biology Communications 71, no. 5 (2015): 531-538. doi: 10.1107/S2053230X15000187. Reproduced in accordance with the original publisher's licensing terms and with permission from the authors.