3L5T

Crystal structure of macrophage migration inhibitory factor (MIF) with thiophenepiperazinylquinolinone inhibitor at 1.86A resolution

Summary for 3L5T

• Entry DOI: 10.2210/pdb3l5t/pdb
• Related: 3L5P 3L5R 3L5S 3L5U 3L5V
• Descriptor: Macrophage migration inhibitory factor, 1-methyl-2-oxo-4-[4-(thiophen-2-ylcarbonyl)piperazin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, SULFATE ION, ... (4 entities in total)
• Functional Keywords: protein-ligand complex, cytokine, cytoplasm, immune response, inflammatory response, innate immunity, isomerase, phosphoprotein, secreted, acetylation
• Biological source: Homo sapiens (human)
• Cellular location: Secreted : P14174
• Total number of polymer chains: 3
• Total formula weight: 40849.20

Authors

McLean, L.,Zhang, Y. (deposition date: 2009-12-22, release date: 2010-03-09, Last modification date: 2023-09-06)

Primary citation

McLean, L.R.,Zhang, Y.,Li, H.,Choi, Y.M.,Han, Z.,Vaz, R.J.,Li, Y.
Fragment screening of inhibitors for MIF tautomerase reveals a cryptic surface binding site.
Bioorg.Med.Chem.Lett., 20:1821-1824, 2010

PubMed Abstract: In the course of a fragment screening campaign by in silico docking followed by X-ray crystallography, a novel binding site for migration inhibitory factor (MIF) inhibitors was demonstrated. The site is formed by rotation of the side-chain of Tyr-36 to reveal a surface binding site in MIF that is hydrophobic and surrounded by aromatic side-chain residues. The crystal structures of two small inhibitors that bind to this site and of a quinolinone inhibitor, that spans the canonical deep pocket near Pro-1 and the new surface binding site, have been solved. These results suggest new opportunities for structure-based design of MIF inhibitors.

PubMed: 20185308
DOI: 10.1016/j.bmcl.2010.02.009

Experimental method

X-RAY DIFFRACTION (1.86 Å)