4DH4

Macrophage migration inhibitory factor Toxoplasma gondii

4DH4 の概要

• エントリーDOI: 10.2210/pdb4dh4/pdb
• 分子名称: MIF, SULFATE ION (3 entities in total)
• 機能のキーワード: trimer, isomerase
• 由来する生物種: Toxoplasma gondii
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12174.95

構造登録者

Richardson, J.M. (登録日: 2012-01-27, 公開日: 2012-11-21, 最終更新日: 2024-02-28)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.82 Å)