title: Fragment screening of inhibitors for MIF tautomerase reveals a cryptic surface binding site.
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.
authors.affiliation: Discovery Research, Sanofi-aventis, Bridgewater, NJ 08807, USA. Larry.Mclean@sanofi-aventis.com
authors.forename: Larry R
authors.initials: LR
authors.lastname: McLean
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Yong-Mi
authors.initials: YM
authors.lastname: Choi
authors.forename: Zuoning
authors.initials: Z
authors.lastname: Han
authors.forename: Roy J
authors.initials: RJ
authors.lastname: Vaz
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D004791:Enzyme Inhibitors; D008263:Macrophage Migration-Inhibitory Factors