Fig. 2

Crystallographic analysis of the MIF-T-614 complex. (A) Alignment of WT MIF (grey cartoon) onto MIF-T-614 (blue cartoon) demonstrates high superposition agreement between the two crystal structures. (B) Analysis of the binding motif of T-614 (orange sticks) showed that the inhibitor predominantly binds on the surface of MIF, blocking the active site opening. For reference, the position of the catalytically active Pro-1 (blue sticks) is provided. (C) Only a small chemical moiety of bound T-614 penetrates the active site. The active site of MIF is illustrated as a dark grey shadow. (D) Stabilizing forces between T-614 and MIF. T-614 forms hydrogen bonds (Lys-32 and Ile-64, black dashed lines, residues shown as sticks), van der Waals interactions (Pro-1, Lys-32, Tyr-36, Ser-63, Ile-64 Trp-108 A and Phe-113 from subunit C and Tyr-95 from subunit B, black lines), and Pi-Pi interactions (Tyr-36, red dashed line) with MIF residues. T614 = iguratimod