1mfi
From Proteopedia
(New page: 200px<br /><applet load="1mfi" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mfi, resolution 1.80Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1mfi.gif|left|200px]]<br /><applet load="1mfi" size=" | + | [[Image:1mfi.gif|left|200px]]<br /><applet load="1mfi" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1mfi, resolution 1.80Å" /> | caption="1mfi, resolution 1.80Å" /> | ||
'''CRYSTAL STRUCTURE OF MACROPHAGE MIGRATION INHIBITORY FACTOR COMPLEXED WITH (E)-2-FLUORO-P-HYDROXYCINNAMATE'''<br /> | '''CRYSTAL STRUCTURE OF MACROPHAGE MIGRATION INHIBITORY FACTOR COMPLEXED WITH (E)-2-FLUORO-P-HYDROXYCINNAMATE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Macrophage migration inhibitory factor (MIF) exhibits dual activities. It | + | Macrophage migration inhibitory factor (MIF) exhibits dual activities. It acts as an immunoregulatory protein as well as a phenylpyruvate tautomerase. To understand better the relationship between these two activities and to elucidate the structural basis for the enzymatic activity, a crystal structure of a complex between murine MIF and (E)-2-fluoro-p-hydroxycinnamate, a competitive inhibitor of the tautomerase activity, has been determined to 1.8 A resolution. The structure is nearly superimposable on that of the free protein indicating that the presence of the inhibitor does not result in any major structural changes. The inhibitor also confirms the location of the active site in a hydrophobic cavity containing the amino-terminal proline. Within this cavity, the inhibitor interacts with residues from adjacent subunits. At the back of the cavity, the side-chain carbonyl oxygen of Asn-97' interacts with the phenolic hydroxyl group of the inhibitor while at the mouth of the cavity the ammonium group of Lys-32 interacts with a carboxylate oxygen. The other carboxylate oxygen of the inhibitor interacts with Pro-1. The hydroxyl group of Tyr-95' interacts weakly with the fluoro group on the inhibitor. The hydrophobic side chains of five active-site residues (Met-2, Ile-64, Met-101, Val-106, and Phe-113) and the phenyl moiety of Tyr-95' are responsible for the binding of the phenyl group. Further insight into the enzymatic activity of MIF was obtained by carrying out kinetic studies using the enol isomers of phenylpyruvate and (p-hydroxyphenyl)pyruvate. The results demonstrate that MIF processes the enol isomers more efficiently than the keto isomers primarily because of a decrease in Km. On the basis of these results, a mechanism is proposed for the MIF-catalyzed tautomerization reaction. |
==About this Structure== | ==About this Structure== | ||
| - | 1MFI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with FHC as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1MFI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=FHC:'>FHC</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MFI OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Czerwinski, R | + | [[Category: Czerwinski, R M.]] |
| - | [[Category: Hackert, M | + | [[Category: Hackert, M L.]] |
| - | [[Category: Jr., W | + | [[Category: Jr., W H.Johnson.]] |
| - | [[Category: Taylor, A | + | [[Category: Taylor, A B.]] |
| - | [[Category: Whitman, C | + | [[Category: Whitman, C P.]] |
[[Category: FHC]] | [[Category: FHC]] | ||
[[Category: cytokine]] | [[Category: cytokine]] | ||
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[[Category: tautomerase]] | [[Category: tautomerase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:54:44 2008'' |
Revision as of 11:54, 21 February 2008
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CRYSTAL STRUCTURE OF MACROPHAGE MIGRATION INHIBITORY FACTOR COMPLEXED WITH (E)-2-FLUORO-P-HYDROXYCINNAMATE
Overview
Macrophage migration inhibitory factor (MIF) exhibits dual activities. It acts as an immunoregulatory protein as well as a phenylpyruvate tautomerase. To understand better the relationship between these two activities and to elucidate the structural basis for the enzymatic activity, a crystal structure of a complex between murine MIF and (E)-2-fluoro-p-hydroxycinnamate, a competitive inhibitor of the tautomerase activity, has been determined to 1.8 A resolution. The structure is nearly superimposable on that of the free protein indicating that the presence of the inhibitor does not result in any major structural changes. The inhibitor also confirms the location of the active site in a hydrophobic cavity containing the amino-terminal proline. Within this cavity, the inhibitor interacts with residues from adjacent subunits. At the back of the cavity, the side-chain carbonyl oxygen of Asn-97' interacts with the phenolic hydroxyl group of the inhibitor while at the mouth of the cavity the ammonium group of Lys-32 interacts with a carboxylate oxygen. The other carboxylate oxygen of the inhibitor interacts with Pro-1. The hydroxyl group of Tyr-95' interacts weakly with the fluoro group on the inhibitor. The hydrophobic side chains of five active-site residues (Met-2, Ile-64, Met-101, Val-106, and Phe-113) and the phenyl moiety of Tyr-95' are responsible for the binding of the phenyl group. Further insight into the enzymatic activity of MIF was obtained by carrying out kinetic studies using the enol isomers of phenylpyruvate and (p-hydroxyphenyl)pyruvate. The results demonstrate that MIF processes the enol isomers more efficiently than the keto isomers primarily because of a decrease in Km. On the basis of these results, a mechanism is proposed for the MIF-catalyzed tautomerization reaction.
About this Structure
1MFI is a Single protein structure of sequence from Mus musculus with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of macrophage migration inhibitory factor complexed with (E)-2-fluoro-p-hydroxycinnamate at 1.8 A resolution: implications for enzymatic catalysis and inhibition., Taylor AB, Johnson WH Jr, Czerwinski RM, Li HS, Hackert ML, Whitman CP, Biochemistry. 1999 Jun 8;38(23):7444-52. PMID:10360941
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