4RV8

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

4RV8 の概要

• エントリーDOI: 10.2210/pdb4rv8/pdb
• 関連するPDBエントリー: 3FFS 4IXH
• 分子名称: 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)
• 機能のキーワード: structural genomics, niaid, national institute of allergy and infectious diseases, center for structural genomics of infectious diseases, csgid, alpha-beta fold, tim barrel, oxidoreductase
• 由来する生物種: Cryptosporidium parvum; 詳細
• 細胞内の位置: Cytoplasm : Q8T6T2
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 157926.68

構造登録者

Kim, Y.,Makowska-Grzyska, M.,Gu, M.,Kavitha, M.,Hedstrom, L.,Anderson, W.F.,Joachimiak, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2014-11-25, 公開日: 2014-12-31, 最終更新日: 2023-12-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.053 Å)