4F2K

Macrophage Migration Inhibitory Factor covalently complexed with phenethylisothiocyanate

Summary for 4F2K

• Entry DOI: 10.2210/pdb4f2k/pdb
• Descriptor: Macrophage migration inhibitory factor, N-(2-phenylethyl)thioformamide, SULFATE ION, ... (5 entities in total)
• Functional Keywords: cytokine, tautomerase, phenethylisothiocyanate, isomerase, isomerase-isomerase inhibitor complex, isomerase/isomerase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P14174
• Total number of polymer chains: 3
• Total formula weight: 38185.57

Authors

Tyndall, J.D.A.,Bernhagen, J.,Hampton, M.B.,Wilbanks, S.M.,Rutledge, M.T. (deposition date: 2012-05-08, release date: 2012-06-06, Last modification date: 2024-11-20)

Primary citation

Tyndall, J.D.A.,Lue, H.,Rutledge, M.T.,Bernhagen, J.,Hampton, M.B.,Wilbanks, S.M.
Macrophage migration inhibitory factor covalently complexed with phenethyl isothiocyanate
Acta Crystallogr.,Sect.F, 68:999-1002, 2012

PubMed Abstract: 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.

PubMed: 22949182
DOI: 10.1107/S1744309112030552

Experimental method

X-RAY DIFFRACTION (1.53 Å)