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1mfi

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Revision as of 08:36, 2 December 2020

CRYSTAL STRUCTURE OF MACROPHAGE MIGRATION INHIBITORY FACTOR COMPLEXED WITH (E)-2-FLUORO-P-HYDROXYCINNAMATE

Structural highlights

1mfi is a 3 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	MIF (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MIF_MOUSE] Pro-inflammatory cytokine. Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Taylor AB, Johnson WH Jr, Czerwinski RM, Li HS, Hackert ML, Whitman CP. 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. Biochemistry. 1999 Jun 8;38(23):7444-52. PMID:10360941 doi:10.1021/bi9904048

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1mfi"

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF MACROPHAGE MIGRATION INHIBITORY FACTOR COMPLEXED WITH (E)-2-FLUORO-P-HYDROXYCINNAMATE==
-<StructureSection load='1mfi' size='340' side='right' caption='[[1mfi]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+<StructureSection load='1mfi' size='340' side='right'caption='[[1mfi]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1mfi]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MFI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1MFI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1mfi]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MFI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1MFI FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FHC:2-FLUORO-3-(4-HYDROXYPHENYL)-2E-PROPENEOATE'>FHC</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FHC:2-FLUORO-3-(4-HYDROXYPHENYL)-2E-PROPENEOATE'>FHC</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MIF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mfi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mfi OCA], [http://pdbe.org/1mfi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1mfi RCSB], [http://www.ebi.ac.uk/pdbsum/1mfi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1mfi ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1mfi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mfi OCA], [http://pdbe.org/1mfi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1mfi RCSB], [http://www.ebi.ac.uk/pdbsum/1mfi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1mfi ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 31: / Line 31: @@
 ==See Also==
-*[[Macrophage inhibitory factor|Macrophage inhibitory factor]]
+*[[Macrophage inhibitory factor 3D structures|Macrophage inhibitory factor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Lk3 transgenic mice]]
 [[Category: Czerwinski, R M]]

1mfi

From Proteopedia

Revision as of 08:36, 2 December 2020

CRYSTAL STRUCTURE OF MACROPHAGE MIGRATION INHIBITORY FACTOR COMPLEXED WITH (E)-2-FLUORO-P-HYDROXYCINNAMATE

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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