1CA7

MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) WITH HYDROXPHENYLPYRUVATE

Summary for 1CA7

• Entry DOI: 10.2210/pdb1ca7/pdb
• Descriptor: PROTEIN (MACROPHAGE MIGRATION INHIBITORY FACTOR), (2E)-2-hydroxy-3-(4-hydroxyphenyl)prop-2-enoic acid (3 entities in total)
• Functional Keywords: protein hormone, cytokine, enzyme
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 3
• Total formula weight: 37605.64

Authors

Lubetsky, J.B.,Lolis, E. (deposition date: 1999-02-25, release date: 1999-06-30, Last modification date: 2025-04-16)

Primary citation

Lubetsky, J.B.,Swope, M.,Dealwis, C.,Blake, P.,Lolis, E.
Pro-1 of macrophage migration inhibitory factor functions as a catalytic base in the phenylpyruvate tautomerase activity.
Biochemistry, 38:7346-7354, 1999

PubMed Abstract: Macrophage migration inhibitory factor (MIF) is an important immunoregulatory molecule with a unique ability to suppress the anti-inflammatory effects of glucocorticoids. Although considered a cytokine, MIF possesses a three-dimensional structure and active site similar to those of 4-oxalocrotonate tautomerase and 5-carboxymethyl-2-hydroxymuconate isomerase. Moreover, a number of catalytic activities have been defined for MIF. To gain insight into the role of catalysis in the biological function of MIF, we have begun to characterize the catalytic activities in more detail. Here we report the crystal structure of MIF complexed with p-hydroxyphenylpyruvate, a substrate for the phenylpyruvate tautomerase activity of MIF. The three binding sites for p-hydroxyphenylpyruvate in the MIF trimer lie at the interface between two subunits. The substrate interacts with Pro-1, Lys-32, and Ile-64 from one subunit and Tyr-95 and Asn-97 from an adjacent subunit. Pro-1 is positioned to function as a catalytic base. There is no functional group that polarizes the alpha-carbonyl of the substrate to weaken the adjacent C-H bond. Mutation of Pro-1 to glycine substantially reduces the catalytic activity. The insertion of an alanine between Pro-1 and Met-2 essentially abolishes activity. Structural studies of these mutants define a source of the reduced activity and provide insight into the mechanism of the catalytic reaction.

PubMed: 10353846
DOI: 10.1021/bi990306m

Experimental method

X-RAY DIFFRACTION (2.5 Å)