4RV8

Co-Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Cryptosporidium parvum and the inhibitor p131

Summary for 4RV8

• Entry DOI: 10.2210/pdb4rv8/pdb
• Related: 3FFS 4IXH
• Descriptor: Inosine-5'-monophosphate dehydrogenase, INOSINIC ACID, 1-(2-{3-[(1E)-N-(2-aminoethoxy)ethanimidoyl]phenyl}propan-2-yl)-3-(4-chloro-3-nitrophenyl)urea, ... (6 entities in total)
• Functional Keywords: structural genomics, niaid, national institute of allergy and infectious diseases, center for structural genomics of infectious diseases, csgid, alpha-beta fold, tim barrel, oxidoreductase
• Biological source: Cryptosporidium parvum; More
• Cellular location: Cytoplasm : Q8T6T2
• Total number of polymer chains: 4
• Total formula weight: 157926.68

Authors

Kim, Y.,Makowska-Grzyska, M.,Gu, M.,Kavitha, M.,Hedstrom, L.,Anderson, W.F.,Joachimiak, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2014-11-25, release date: 2014-12-31, Last modification date: 2023-12-06)

Primary citation

Kim, Y.,Makowska-Grzyska, M.,Gorla, S.K.,Gollapalli, D.R.,Cuny, G.D.,Joachimiak, A.,Hedstrom, L.
Structure of Cryptosporidium IMP dehydrogenase bound to an inhibitor with in vivo antiparasitic activity.
Acta Crystallogr F Struct Biol Commun, 71:531-538, 2015

PubMed Abstract: Inosine 5'-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 5'-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.

PubMed: 25945705
DOI: 10.1107/S2053230X15000187

Experimental method

X-RAY DIFFRACTION (2.053 Å)