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| - | [[Image:1ca7.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1ca7| PDB=1ca7 | SCENE= }} | | {{STRUCTURE_1ca7| PDB=1ca7 | SCENE= }} |
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| - | '''MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) WITH HYDROXPHENYLPYRUVATE'''
| + | ===MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) WITH HYDROXPHENYLPYRUVATE=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10353846}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10353846 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10353846}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Enzyme]] | | [[Category: Enzyme]] |
| | [[Category: Protein hormone]] | | [[Category: Protein hormone]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 12:31:09 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 20:26:52 2008'' |
Revision as of 17:26, 30 June 2008
Template:STRUCTURE 1ca7
MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) WITH HYDROXPHENYLPYRUVATE
Template:ABSTRACT PUBMED 10353846
About this Structure
1CA7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Pro-1 of macrophage migration inhibitory factor functions as a catalytic base in the phenylpyruvate tautomerase activity., Lubetsky JB, Swope M, Dealwis C, Blake P, Lolis E, Biochemistry. 1999 Jun 1;38(22):7346-54. PMID:10353846
Page seeded by OCA on Mon Jun 30 20:26:52 2008
