3B64

Macrophage Migration Inhibitory Factor (MIF) From /Leishmania Major

Summary for 3B64

• Entry DOI: 10.2210/pdb3b64/pdb
• Related: 1MIF 2OS5
• Descriptor: Macrophage migration inhibitory factor-like protein, ISOPROPYL ALCOHOL (3 entities in total)
• Functional Keywords: cytokine, leishmania, macrophage migration inhibitory factor, mif, lm1740mif, lmmif, unknown function
• Biological source: Leishmania major
• Total number of polymer chains: 1
• Total formula weight: 12455.25

Authors

Zierow, S.,Cho, Y.,Lolis, E. (deposition date: 2007-10-27, release date: 2008-06-10, Last modification date: 2024-02-21)

Primary citation

Kamir, D.,Zierow, S.,Leng, L.,Cho, Y.,Diaz, Y.,Griffith, J.,McDonald, C.,Merk, M.,Mitchell, R.A.,Trent, J.,Chen, Y.,Kwong, Y.K.,Xiong, H.,Vermeire, J.,Cappello, M.,McMahon-Pratt, D.,Walker, J.,Bernhagen, J.,Lolis, E.,Bucala, R.
A leishmania ortholog of macrophage migration inhibitory factor modulates host macrophage responses.
J.Immunol., 180:8250-8261, 2008

PubMed Abstract: Parasitic organisms have evolved specialized strategies to evade immune defense mechanisms. We describe herein an ortholog of the cytokine, macrophage migration inhibitory factor (MIF), which is produced by the obligate intracellular parasite, Leishmania major. The Leishmania MIF protein, Lm1740MIF, shows significant structural homology with human MIF as revealed by a high-resolution x-ray crystal structure (1.03 A). Differences between the two proteins in the N-terminal tautomerization site are evident, and we provide evidence for the selective, species-specific inhibition of MIF by small-molecule antagonists that target this site. Lm1740MIF shows significant binding interaction with the MIF receptor, CD74 (K(d) = 2.9 x 10(-8) M). Like its mammalian counterpart, Lm1740MIF induces ERK1/2 MAP kinase activation in a CD74-dependent manner and inhibits the activation-induced apoptosis of macrophages. The ability of Lm1740MIF to inhibit apoptosis may facilitate the persistence of Leishmania within the macrophage and contribute to its evasion from immune destruction.

PubMed: 18523291

Experimental method

X-RAY DIFFRACTION (1.03 Å)