Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1371912 | Bioorganic & Medicinal Chemistry Letters | 2010 | 4 Pages |
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.
Graphical abstractFragment screening by in silico docking followed by X-ray crystallography demonstrates the formation of a previously unreported surface binding site in MIF that is hydrophobic and surrounded by aromatic side-chain residues.Figure optionsDownload full-size imageDownload as PowerPoint slide