7kqx
From Proteopedia
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==MIF Y99C homotrimeric mutant== | ==MIF Y99C homotrimeric mutant== | ||
| - | <StructureSection load='7kqx' size='340' side='right'caption='[[7kqx]]' scene=''> | + | <StructureSection load='7kqx' size='340' side='right'caption='[[7kqx]], [[Resolution|resolution]] 1.60Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KQX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KQX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7kqx]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KQX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KQX FirstGlance]. <br> |
| - | </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=7kqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kqx OCA], [https://pdbe.org/7kqx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kqx RCSB], [https://www.ebi.ac.uk/pdbsum/7kqx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kqx ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=7kqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kqx OCA], [https://pdbe.org/7kqx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kqx RCSB], [https://www.ebi.ac.uk/pdbsum/7kqx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kqx ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/MIF_HUMAN MIF_HUMAN] Genetic variations in MIF are associated with susceptibility to rheumatoid arthritis systemic juvenile (RASJ) [MIM:[https://omim.org/entry/604302 604302]. An inflammatory articular disorder with systemic-onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MIF_HUMAN MIF_HUMAN] 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.<ref>PMID:15908412</ref> <ref>PMID:17443469</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Macrophage migration inhibitory factor (MIF) is an inflammatory protein with various non-overlapping functions. It is not only conserved in mammals, but it is found in parasites, fish, and plants. Human MIF is a homotrimer with an enzymatic cavity between two subunits with Pro1 as a catalytic base, activates the receptors CD74, CXCR2, and CXCR4, has functional interactions in the cytosol, and is reported to be a nuclease. There is a solvent channel down its 3-fold axis with a recently identified gating residue as an allosteric site important for regulating, to different extents, the enzymatic activity and CD74 binding and signaling. In this study we explore the consequence of converting the allosteric residue Tyr99 to cysteine (Y99C) and characterize its crystallographic structure, NMR dynamics, stability, CD74 function, and enzymatic activity. In addition to the homotrimeric variant, we develop strategies for expressing and purifying a heterotrimeric variant consisting of mixed wild type and Y99C for characterization of the allosteric site to provide more insight. | ||
| + | |||
| + | A Cysteine Variant at an Allosteric Site Alters MIF Dynamics and Biological Function in Homo- and Heterotrimeric Assemblies.,Skeens E, Pantouris G, Shah D, Manjula R, Ombrello MJ, Maluf NK, Bhandari V, Lisi GP, Lolis EJ Front Mol Biosci. 2022 Feb 8;9:783669. doi: 10.3389/fmolb.2022.783669. , eCollection 2022. PMID:35252348<ref>PMID:35252348</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7kqx" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Georgios P]] | [[Category: Georgios P]] | ||
[[Category: Lolis EJ]] | [[Category: Lolis EJ]] | ||
[[Category: Manjula R]] | [[Category: Manjula R]] | ||
Revision as of 12:04, 1 February 2023
MIF Y99C homotrimeric mutant
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