4dh4: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Macrophage migration inhibitory factor Toxoplasma gondii== | |||
===Macrophage migration inhibitory factor Toxoplasma gondii | <StructureSection load='4dh4' size='340' side='right' caption='[[4dh4]], [[Resolution|resolution]] 1.82Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4dh4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DH4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DH4 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TGGT1_032990, TGME49_090040, TGVEG_083780 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5811 Toxoplasma gondii])</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=4dh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dh4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dh4 RCSB], [http://www.ebi.ac.uk/pdbsum/4dh4 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Macrophage migration inhibitory factor (MIF) is a proinflammatory molecule in mammals that, unusually for a cytokine, exhibits tautomerase and oxidoreductase enzymatic activities. Homologues of this well conserved protein are found within diverse phyla including a number of parasitic organisms. Herein, we produced recombinant histidine-tagged Toxoplasma gondii MIF (TgMIF), a 12-kDa protein that lacks oxidoreductase activity but exhibits tautomerase activity with a specific activity of 19.3 mumol/min/mg that cannot be inhibited by the human MIF inhibitor ISO-1. The crystal structure of the TgMIF homotrimer has been determined to 1.82 A, and although it has close structural homology with mammalian MIFs, it has critical differences in the tautomerase active site that account for the different inhibitor sensitivity. We also demonstrate that TgMIF can elicit IL-8 production from human peripheral blood mononuclear cells while also activating ERK MAPK pathways in murine bone marrow-derived macrophages. TgMIF may therefore play an immunomodulatory role during T. gondii infection in mammals. | |||
Biochemical and Immunological Characterization of Toxoplasma gondii Macrophage Migration Inhibitory Factor.,Sommerville C, Richardson JM, Williams RA, Mottram JC, Roberts CW, Alexander J, Henriquez FL J Biol Chem. 2013 May 3;288(18):12733-41. doi: 10.1074/jbc.M112.419911. Epub 2013, Feb 26. PMID:23443656<ref>PMID:23443656</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Phenylpyruvate tautomerase]] | [[Category: Phenylpyruvate tautomerase]] | ||
[[Category: Toxoplasma gondii]] | [[Category: Toxoplasma gondii]] | ||
[[Category: Richardson, J M | [[Category: Richardson, J M]] | ||
[[Category: Isomerase]] | [[Category: Isomerase]] | ||
[[Category: Trimer]] | [[Category: Trimer]] | ||
Revision as of 11:42, 21 December 2014
Macrophage migration inhibitory factor Toxoplasma gondiiMacrophage migration inhibitory factor Toxoplasma gondii
Structural highlights
Publication Abstract from PubMedMacrophage migration inhibitory factor (MIF) is a proinflammatory molecule in mammals that, unusually for a cytokine, exhibits tautomerase and oxidoreductase enzymatic activities. Homologues of this well conserved protein are found within diverse phyla including a number of parasitic organisms. Herein, we produced recombinant histidine-tagged Toxoplasma gondii MIF (TgMIF), a 12-kDa protein that lacks oxidoreductase activity but exhibits tautomerase activity with a specific activity of 19.3 mumol/min/mg that cannot be inhibited by the human MIF inhibitor ISO-1. The crystal structure of the TgMIF homotrimer has been determined to 1.82 A, and although it has close structural homology with mammalian MIFs, it has critical differences in the tautomerase active site that account for the different inhibitor sensitivity. We also demonstrate that TgMIF can elicit IL-8 production from human peripheral blood mononuclear cells while also activating ERK MAPK pathways in murine bone marrow-derived macrophages. TgMIF may therefore play an immunomodulatory role during T. gondii infection in mammals. Biochemical and Immunological Characterization of Toxoplasma gondii Macrophage Migration Inhibitory Factor.,Sommerville C, Richardson JM, Williams RA, Mottram JC, Roberts CW, Alexander J, Henriquez FL J Biol Chem. 2013 May 3;288(18):12733-41. doi: 10.1074/jbc.M112.419911. Epub 2013, Feb 26. PMID:23443656[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||||