3RF4

Ancylostoma ceylanicum mif in complex with furosemide

3RF4 の概要

• エントリーDOI: 10.2210/pdb3rf4/pdb
• 関連するPDBエントリー: 2OS5 3RF5
• 分子名称: Macrophage migration inhibitory factor, 5-(AMINOSULFONYL)-4-CHLORO-2-[(2-FURYLMETHYL)AMINO]BENZOIC ACID, IMIDAZOLE, ... (6 entities in total)
• 機能のキーワード: protein-small molecule complex, isomerase, isomerase-isomerase inhibitor complex, isomerase/isomerase inhibitor
• 由来する生物種: Ancylostoma ceylanicum
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 40476.38

構造登録者

Cho, Y.,Lolis, E. (登録日: 2011-04-05, 公開日: 2011-10-12, 最終更新日: 2023-09-13)

主引用文献

Cho, Y.,Vermeire, J.J.,Merkel, J.S.,Leng, L.,Du, X.,Bucala, R.,Cappello, M.,Lolis, E.
Drug Repositioning and Pharmacophore Identification in the Discovery of Hookworm MIF Inhibitors.
Chem.Biol., 18:1089-1101, 2011

PubMed Abstract: The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new pharmacophores. Hookworms are blood-feeding, intestinal nematode parasites that infect up to 600 million people worldwide. Vaccination with recombinant Ancylostoma ceylanicum macrophage migration inhibitory factor (rAceMIF) provided partial protection from disease, thus establishing a "proof-of-concept" for targeting AceMIF to prevent or treat infection. A high-throughput screen (HTS) against rAceMIF identified six AceMIF-specific inhibitors. A nonsteroidal anti-inflammatory drug (NSAID), sodium meclofenamate, could be tested in an animal model to assess the therapeutic efficacy in treating hookworm disease. Furosemide, an FDA-approved diuretic, exhibited submicromolar inhibition of rAceMIF tautomerase activity. Structure-activity relationships of a pharmacophore based on furosemide included one analog that binds similarly to the active site, yet does not inhibit the Na-K-Cl symporter (NKCC1) responsible for diuretic activity.

PubMed: 21944748
DOI: 10.1016/j.chembiol.2011.07.011

実験手法

X-RAY DIFFRACTION (1.8 Å)