3RF4
Ancylostoma ceylanicum mif in complex with furosemide
Summary for 3RF4
| Entry DOI | 10.2210/pdb3rf4/pdb |
| Related | 2OS5 3RF5 |
| Descriptor | Macrophage migration inhibitory factor, 5-(AMINOSULFONYL)-4-CHLORO-2-[(2-FURYLMETHYL)AMINO]BENZOIC ACID, IMIDAZOLE, ... (6 entities in total) |
| Functional Keywords | protein-small molecule complex, isomerase, isomerase-isomerase inhibitor complex, isomerase/isomerase inhibitor |
| Biological source | Ancylostoma ceylanicum |
| Total number of polymer chains | 3 |
| Total formula weight | 40476.38 |
| Authors | |
| Primary citation | 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 Cited by 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: 21944748DOI: 10.1016/j.chembiol.2011.07.011 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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