4DH4

Macrophage migration inhibitory factor Toxoplasma gondii

Summary for 4DH4

• Entry DOI: 10.2210/pdb4dh4/pdb
• Descriptor: MIF, SULFATE ION (3 entities in total)
• Functional Keywords: trimer, isomerase
• Biological source: Toxoplasma gondii
• Total number of polymer chains: 1
• Total formula weight: 12174.95

Authors

Richardson, J.M. (deposition date: 2012-01-27, release date: 2012-11-21, Last modification date: 2024-02-28)

Primary citation

Sommerville, C.,Richardson, J.M.,Williams, R.A.,Mottram, J.C.,Roberts, C.W.,Alexander, J.,Henriquez, F.L.
Biochemical and Immunological Characterization of Toxoplasma gondii Macrophage Migration Inhibitory Factor.
J.Biol.Chem., 288:12733-12741, 2013

PubMed Abstract: Macrophage migration inhibitory factor (MIF) is a proinflammatory molecule in mammals that, unusually for a cytokine, exhibits tautomerase and oxidoreductase enzymatic activities. Homologues of this well conserved protein are found within diverse phyla including a number of parasitic organisms. Herein, we produced recombinant histidine-tagged Toxoplasma gondii MIF (TgMIF), a 12-kDa protein that lacks oxidoreductase activity but exhibits tautomerase activity with a specific activity of 19.3 μmol/min/mg that cannot be inhibited by the human MIF inhibitor ISO-1. The crystal structure of the TgMIF homotrimer has been determined to 1.82 Å, and although it has close structural homology with mammalian MIFs, it has critical differences in the tautomerase active site that account for the different inhibitor sensitivity. We also demonstrate that TgMIF can elicit IL-8 production from human peripheral blood mononuclear cells while also activating ERK MAPK pathways in murine bone marrow-derived macrophages. TgMIF may therefore play an immunomodulatory role during T. gondii infection in mammals.

PubMed: 23443656
DOI: 10.1074/jbc.M112.419911

Experimental method

X-RAY DIFFRACTION (1.82 Å)