5B4O

Crystal structure of Macrophage Migration Inhibitory Factor in complex with BTZO-14

Summary for 5B4O

• Entry DOI: 10.2210/pdb5b4o/pdb
• Descriptor: Macrophage migration inhibitory factor, 2-pyridin-3-yl-1,3-benzothiazin-4-one, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: isomerase
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted : P14174
• Total number of polymer chains: 3
• Total formula weight: 38952.92

Authors

Oki, H.,Igaki, S.,Moriya, Y.,Hayano, Y.,Habuka, N. (deposition date: 2016-04-07, release date: 2016-04-20, Last modification date: 2023-11-08)

Primary citation

Kimura, H.,Sato, Y.,Tajima, Y.,Suzuki, H.,Yukitake, H.,Imaeda, T.,Kajino, M.,Oki, H.,Takizawa, M.,Tanida, S.
BTZO-1, a cardioprotective agent, reveals that macrophage migration inhibitory factor regulates ARE-mediated gene expression
Chem. Biol., 17:1282-1294, 2010

PubMed Abstract: In a screening program to discover therapeutic drugs for heart diseases, we identified BTZO-1, a 1,3-benzothiazin-4-one derivative, which activated antioxidant response element (ARE)-mediated gene expression and suppressed oxidative stress-induced cardiomyocyte apoptosis in vitro. An active BTZO-1 derivative for ARE-activation protected heart tissue during ischemia/reperfusion injury in rats. Macrophage migration inhibitory factor (MIF), which is known to protect cells from oxidative insult, was identified as a specific BTZO-1-binding protein. BTZO-1 binds to MIF with a K(d) of 68.6 nM, and its binding required the intact N-terminal Pro1. MIF, in the presence of BTZO-1, activated the glutathione S-transferase Ya subunit (GST Ya) gene ARE, whereas reduction of cellular MIF protein levels by siRNA suppressed BTZO-1-induced GST Ya expression. These results suggest that BTZO-1 activates the GST Ya gene ARE by interacting with MIF.

PubMed: 21168764
DOI: 10.1016/j.chembiol.2010.10.011

Experimental method

X-RAY DIFFRACTION (1.37 Å)