1LJT

Crystal Structure of Macrophage Migration Inhibitory Factor complexed with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole-acetic acid methyl ester (ISO-1)

Summary for 1LJT

• Entry DOI: 10.2210/pdb1ljt/pdb
• Descriptor: Macrophage migration inhibitory factor, 3-(4-HYDROXYPHENYL)-4,5-DIHYDRO-5-ISOXAZOLE-ACETIC ACID METHYL ESTER (3 entities in total)
• Functional Keywords: protein-inhibitor complex, immune system
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P14174
• Total number of polymer chains: 3
• Total formula weight: 37770.88

Authors

Lubetsky, J.B.,Dios, A.,Han, J.,Aljabari, B.,Ruzsicska, B.,Mitchell, R.,Lolis, E.,Al-Abed, Y. (deposition date: 2002-04-22, release date: 2002-11-27, Last modification date: 2024-02-14)

Primary citation

Lubetsky, J.B.,Dios, A.,Han, J.,Aljabari, B.,Ruzsicska, B.,Mitchell, R.,Lolis, E.,Al-Abed, Y.
The Tautomerase Active Site of Macrophage Migration Inhibitory factor is a Potential Target for Discovery of Novel Anti-inflammatory Agents
J.Biol.Chem., 277:24976-24982, 2002

PubMed Abstract: 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 vitro glucocorticoid 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 MIF d-dopachrome tautomerase activity, reveals that ISO-1 binds to the same position of the active site as p-hydroxyphenylpyruvic acid, a substrate of MIF. ISO-1 inhibits several MIF biological activities, further establishing a role for the catalytic active site of MIF.

PubMed: 11997397
DOI: 10.1074/jbc.M203220200

Experimental method

X-RAY DIFFRACTION (2 Å)