Open AccessMacrophage migration inhibitory factor covalently complexed with phenethyl isothiocyanate
Author(s) -
Tyndall Joel D. A.,
Lue Hongqi,
Rutledge Malcolm T.,
Bernhagen Jurgen,
Hampton Mark B.,
Wilbanks Sigurd M.
Publication year - 2012
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309112030552
Subject(s) - phenethyl isothiocyanate , covalent bond , macrophage migration inhibitory factor , isothiocyanate , chemistry , inhibitory postsynaptic potential , fluorescein isothiocyanate , structure–activity relationship , macrophage , stereochemistry , chemical modification , biochemistry , conformational change , in vitro , biology , fluorescence , immunology , organic chemistry , physics , quantum mechanics , neuroscience , cytokine
Macrophage migration inhibitory factor is irreversibly inhibited via covalent modification by phenethyl isothiocyanate, a naturally occurring compound with anti‐inflammatory and anticancer properties. The structure of the modified protein obtained from X‐ray diffraction data to 1.64 Å resolution is presented. The inhibitor sits within a deep hydrophobic pocket between subunits of the homotrimer and is highly ordered. The secondary structure of macrophage migratory inhibitory factor is unchanged by this modification, but there are significant rearrangements, including of the side‐chain position of Tyr37 and the main chain of residues 31–34. These changes may explain the decreased binding of the modified protein to the receptor CD74. Together with the pocket, the areas of conformational change define specific targets for the design of more selective and potent inhibitors as potential therapeutics.
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