1ljt
From Proteopedia
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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)
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Persistent Mullerian duct syndrome, type I OMIM:[600957], Rheumatoid arthritis, systemic juvenile, susceptibility to OMIM:[153620]
About this Structure
1LJT is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
The tautomerase active site of macrophage migration inhibitory factor is a potential target for discovery of novel anti-inflammatory agents., Lubetsky JB, Dios A, Han J, Aljabari B, Ruzsicska B, Mitchell R, Lolis E, Al-Abed Y, J Biol Chem. 2002 Jul 12;277(28):24976-82. Epub 2002 May 7. PMID:11997397
Page seeded by OCA on Fri Feb 15 16:18:50 2008
