Structure of Cryptosporidium IMP dehydrogenase bound to an inhibitor with in vivo antiparasitic activity
Inosine 5'-monophosphate dehydrogenase (IMPDH) is a promising target for the treatment ofCryptosporidiuminfections. Here, the structure ofC. parvumIMPDH (CpIMPDH) in complex with inosine 5'-monophosphate (IMP) and P131, an inhibitor within vivoanticryptosporidial 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 NO2moieties 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 ofC. parvuminhibitors for both antiparasitic and antibacterial applications.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- National Institutes of Health (NIH) - National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH); USDOE Office of Science - Office of Biological and Environmental Research
- DOE Contract Number:
- AC02-06CH11357
- OSTI ID:
- 1391805
- Journal Information:
- Acta Crystallographica. Section F, Structural Biology Communications, Vol. 71, Issue 5; ISSN 2053-230X
- Publisher:
- International Union of Crystallography
- Country of Publication:
- United States
- Language:
- English
Inhibitors of inosine 5′-monophosphate dehydrogenase as emerging new generation antimicrobial agents
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journal | January 2019 |
Cryptosporidium in humans and animals-a one health approach to prophylaxis
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journal | September 2016 |
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