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2gdg

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Revision as of 07:21, 20 June 2018

Crystal structure of covalently modified macrophage inhibitory factor

Structural highlights

2gdg 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.
Related:	1mif, 1mff, 1mfi, 1ca7, 1p1g, 1cgq, 1gcz
Gene:	Mif (LK3 transgenic mice)
Activity:	Phenylpyruvate tautomerase, with EC number 5.3.2.1
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) is an important immunoregulatory protein that has been implicated in several inflammatory diseases. MIF also has a phenylpyruvate tautomerase (PPT) activity, the role of which remains elusive in these biological activities. The acetylene compound, 2-oxo-4-phenyl-3-butynoate (2-OPB), has been synthesized and tested as a potential irreversible inhibitor of its enzymatic activity. Incubation of the compound with MIF results in the rapid and irreversible loss of the PPT activity. Mass spectral analysis established that the amino-terminal proline, previously implicated as a catalytic base in the PPT-catalyzed reaction, is the site of covalent modification. Inactivation of the PPT activity likely occurs by a Michael addition of Pro-1 to C-4 of the inhibitor. Attempts to crystallize the inactivated complex to confirm the structure of the adduct on the covalently modified Pro-1 by X-ray crystallography were not successful. Nor was it possible to unambiguously interpret electron density observed in the active sites of the native crystals soaked with the inhibitor. This may be due to crystal packing in that the side chain of Glu-16 from an adjacent trimer occupies one active site. However, this crystal contact may be partially responsible for the high-resolution quality of these MIF crystals. Nonetheless, because MIF is a member of the tautomerase superfamily, a group of structurally homologous proteins that share a beta-alpha-beta structural motif and a catalytic Pro-1, 2-OPB may find general use as a probe of tautomerase superfamily members that function as PPTs.

Inactivation of the phenylpyruvate tautomerase activity of macrophage migration inhibitory factor by 2-oxo-4-phenyl-3-butynoate.,Golubkov PA, Johnson WH Jr, Czerwinski RM, Person MD, Wang SC, Whitman CP, Hackert ML Bioorg Chem. 2006 Aug;34(4):183-99. Epub 2006 Jun 14. PMID:16780921^[1]

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

References

↑ Golubkov PA, Johnson WH Jr, Czerwinski RM, Person MD, Wang SC, Whitman CP, Hackert ML. Inactivation of the phenylpyruvate tautomerase activity of macrophage migration inhibitory factor by 2-oxo-4-phenyl-3-butynoate. Bioorg Chem. 2006 Aug;34(4):183-99. Epub 2006 Jun 14. PMID:16780921 doi:10.1016/j.bioorg.2006.05.001

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/2gdg"

@@ Line 1: / Line 1: @@
 ==Crystal structure of covalently modified macrophage inhibitory factor==
 <StructureSection load='2gdg' size='340' side='right' caption='[[2gdg]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phenylpyruvate_tautomerase Phenylpyruvate tautomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.2.1 5.3.2.1] </span></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=2gdg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gdg OCA], [http://pdbe.org/2gdg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2gdg RCSB], [http://www.ebi.ac.uk/pdbsum/2gdg PDBsum]</span></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=2gdg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gdg OCA], [http://pdbe.org/2gdg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2gdg RCSB], [http://www.ebi.ac.uk/pdbsum/2gdg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2gdg ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gd/2gdg_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gd/2gdg_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

2gdg

From Proteopedia

Revision as of 07:21, 20 June 2018

Crystal structure of covalently modified macrophage inhibitory factor

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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