1ca7
From Proteopedia
(New page: 200px<br /> <applet load="1ca7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ca7, resolution 2.5Å" /> '''MACROPHAGE MIGRATION...) |
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| - | [[Image:1ca7.gif|left|200px]]<br /> | + | [[Image:1ca7.gif|left|200px]]<br /><applet load="1ca7" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ca7" size=" | + | |
caption="1ca7, resolution 2.5Å" /> | caption="1ca7, resolution 2.5Å" /> | ||
'''MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) WITH HYDROXPHENYLPYRUVATE'''<br /> | '''MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) WITH HYDROXPHENYLPYRUVATE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Macrophage migration inhibitory factor (MIF) is an important | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1CA7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ENO as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1CA7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ENO:'>ENO</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CA7 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Lolis, E.]] | [[Category: Lolis, E.]] | ||
| - | [[Category: Lubetsky, J | + | [[Category: Lubetsky, J B.]] |
[[Category: ENO]] | [[Category: ENO]] | ||
[[Category: cytokine]] | [[Category: cytokine]] | ||
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[[Category: protein hormone]] | [[Category: protein hormone]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:04:02 2008'' |
Revision as of 10:04, 21 February 2008
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MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) WITH HYDROXPHENYLPYRUVATE
Contents |
Overview
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.
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
1CA7 is a Single protein structure of sequence from Homo sapiens with as ligand. 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 Thu Feb 21 12:04:02 2008
Categories: Homo sapiens | Single protein | Lolis, E. | Lubetsky, J B. | ENO | Cytokine | Enzyme | Protein hormone
