Ternary Complex of Macrophage Migration Inhibitory Factor (MIF) Bound Both to 4-hydroxyphenylpyruvate and to the Allosteric Inhibitor AV1013 (R-stereoisomer)

(2E)-2-hydroxy-3-(4-hydroxyphenyl)prop-2-enoic acid

Allosteric inhibition of macrophage migration inhibitory factor revealed by ibudilast.

MIF, Phenylpyruvate tautomerase, L-dopachrome tautomerase, L-dopachrome isomerase, Glycosylation-inhibiting factor, GIF

2 M ammonium sulfate, 3% isopropanol, 0.5 M NaCl, 0.1 M tris(hydroxymethyl)aminomethane; mixed in a 1:1 ratio with the protein:substrate:inhibitor complex, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 310K

Binary complex of MIF Bound to (R)-AV1013 in the absence of substrate

MOLECULE ENO 901 CHAIN C COULD NOT BE THE ENOL TAUTOMER, DUE TO THE DIHEDRAL ANGLE BETWEEN C2 AND C3 OF THE PYRUVATE NOT ALLOWING A DOUBLE BOND, BUT WITH THE BOND ANGLE AT ATOM C3 TOO WIDE FOR THE KETO TAUTOMER. THEREFORE, ACCORDING TO THE ELECTRON DENSITY (WHICH HAS HIGH RESOLUTION) IT WOULD APPEAR AS IF IT IS SOME FORM OF INTERMEDIATE.

HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. U VALUES: REFINED INDIVIDUALLY

Macrophage migration inhibitory factor (E.C.5.3.2.1, 5.3.3.12)

allosteric inhibition, Cytokine, Immune response, Inflammatory response, Innate immunity, Isomerase, Phosphoprotein, Secreted