2gdg

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /><applet load="2gdg" size="450" color="white" frame="true" align="right" spinBox="true" caption="2gdg, resolution 1.45&Aring;" /> '''Crystal structure of...)
Current revision (09:39, 30 August 2023) (edit) (undo)
 
(14 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2gdg.gif|left|200px]]<br /><applet load="2gdg" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="2gdg, resolution 1.45&Aring;" />
 
-
'''Crystal structure of covalently modified macrophage inhibitory factor'''<br />
 
-
==Overview==
+
==Crystal structure of covalently modified macrophage inhibitory factor==
-
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.
+
<StructureSection load='2gdg' size='340' side='right'caption='[[2gdg]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[2gdg]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GDG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GDG FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.45&#8491;</td></tr>
 +
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2gdg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gdg OCA], [https://pdbe.org/2gdg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gdg RCSB], [https://www.ebi.ac.uk/pdbsum/2gdg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gdg ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/MIF_MOUSE 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 ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<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>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2gdg ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== 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.
-
==About this Structure==
+
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<ref>PMID:16780921</ref>
-
2GDG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2GDG OCA].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16780921 16780921]
+
</div>
-
[[Category: Mus musculus]]
+
<div class="pdbe-citations 2gdg" style="background-color:#fffaf0;"></div>
-
[[Category: Phenylpyruvate tautomerase]]
+
-
[[Category: Single protein]]
+
-
[[Category: Golubkov, P.A.]]
+
-
[[Category: Hackert, M.L.]]
+
-
[[Category: pro-1 pucker]]
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 11:08:24 2007''
+
==See Also==
 +
*[[Macrophage inhibitory factor 3D structures|Macrophage inhibitory factor 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Large Structures]]
 +
[[Category: Mus musculus]]
 +
[[Category: Golubkov PA]]
 +
[[Category: Hackert ML]]

Current revision

Crystal structure of covalently modified macrophage inhibitory factor

PDB ID 2gdg

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2gdg"
Personal tools