3KHJ

C. parvum inosine monophosphate dehydrogenase bound by inhibitor C64

3KHJ の概要

• エントリーDOI: 10.2210/pdb3khj/pdb
• 関連するPDBエントリー: 1LRT 1NF7 1NFB 1PVN 1ZFJ
• 分子名称: Inosine-5-monophosphate dehydrogenase, INOSINIC ACID, N-(4-bromophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide, ... (5 entities in total)
• 機能のキーワード: enzyme-inhibitor complex, oxidoreductase
• 由来する生物種: Cryptosporidium parvum; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 312216.09

構造登録者

MacPherson, I.S.,Hedstrom, L.K. (登録日: 2009-10-30, 公開日: 2010-02-02, 最終更新日: 2024-02-21)

主引用文献

Macpherson, I.S.,Kirubakaran, S.,Gorla, S.K.,Riera, T.V.,D'Aquino, J.A.,Zhang, M.,Cuny, G.D.,Hedstrom, L.
The structural basis of Cryptosporidium -specific IMP dehydrogenase inhibitor selectivity.
J.Am.Chem.Soc., 132:1230-1231, 2010

PubMed Abstract: Cryptosporidium parvum is a potential biowarfare agent, an important AIDS pathogen, and a major cause of diarrhea and malnutrition. No vaccines or effective drug treatment exist to combat Cryptosporidium infection. This parasite relies on inosine 5'-monophosphate dehydrogenase (IMPDH) to obtain guanine nucleotides, and inhibition of this enzyme blocks parasite proliferation. Here, we report the first crystal structures of CpIMPDH. These structures reveal the structural basis of inhibitor selectivity and suggest a strategy for further optimization. Using this information, we have synthesized low-nanomolar inhibitors that display 10(3) selectivity for the parasite enzyme over human IMPDH2.

PubMed: 20052976
DOI: 10.1021/ja909947a

実験手法

X-RAY DIFFRACTION (2.8 Å)