| Autor: |
Lubetsky, Jodi B., Dios, Angeles, Han, Jialian, Aljabari, Bayan, Ruzsicska, Bela, Mitchell, Robert, Lolis, Elias, Al-Abed, Yousef |
| Zdroj: |
Journal of Biological Chemistry; July 2002, Vol. 277 Issue: 28 p24976-24982, 7p |
| Abstrakt: |
Macrophage migration inhibitory factor (MIF) is an immunoregulatory protein that is a potential therapeutic target for a number of inflammatory diseases. Evidence exists that an unexpected catalytic active site of MIF may have a biological function. To gain further insight into the role of the catalytic active site, a series of mutational, structural, and biological activity studies were performed. The insertion of an alanine between Pro-1 and Met-2 (PAM) abolishes a non-physiological catalytic activity, and this mutant is defective in the in vitroglucocorticoid counter-regulatory activity of MIF. The crystal structure of MIF complexed to (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), an inhibitor of MIFd-dopachrome tautomerase activity, reveals that ISO-1 binds to the same position of the active site asp-hydroxyphenylpyruvic acid, a substrate of MIF. ISO-1 inhibits several MIF biological activities, further establishing a role for the catalytic active site of MIF. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
