View source for 7e45


==Crystal structure of compound 7 bound to MIF==
<StructureSection load='7e45' size='340' side='right'caption='[[7e45]], [[Resolution|resolution]] 1.43&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7e45]] 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=7E45 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E45 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]] 1.433&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HWO:(2R)-7-[(2R,3R,4R,5S,6S)-6-(hydroxymethyl)-3-[(2R,3R,4R,5R,6S)-6-methyl-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-4,5-bis(oxidanyl)oxan-2-yl]oxy-2-(4-methoxy-3-oxidanyl-phenyl)-5-oxidanyl-2,3-dihydrochromen-4-one'>HWO</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=7e45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e45 OCA], [https://pdbe.org/7e45 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e45 RCSB], [https://www.ebi.ac.uk/pdbsum/7e45 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e45 ProSAT]</span></td></tr>
</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 ==
Dietary flavonoids are known to have anti-inflammatory and anticancer effects, but their influences on human macrophage migration inhibitory factor (MIF), a vital proinflammatory cytokine recognized as a therapeutic target for infectious diseases and cancers, have been rarely reported. Here, we identified 24 dietary flavonoids that could inhibit the tautomerase activity of MIF, five of which exerted IC(50) values lower than the positive control ISO-1 in the micromolar range: morin (IC(50) = 11.01 +/- 0.45 muM) and amentoflavone (IC(50) = 13.32 +/- 0.64 muM) exhibited the most potent efficacy followed by apigenin (IC(50) = 42.74 +/- 4.20 muM), naringin (IC(50) = 51.38 +/- 2.12 muM), and fisetin (IC(50) = 51.99 +/- 0.63 muM). X-ray crystallography, molecular docking, and cellular experiments were utilized to illustrate the molecular binding details and structure-activity relationships. Scaffold modifications of flavonoids significantly influenced the potency. What stands out for morin is the unique 2'-OH substitution. In addition, amentoflavone situated at the MIF trimer pore may impact MIF-CD74 signaling. The results also showed that flavonoids could suppress cell chemotaxis and nitric oxide production in RAW264.7 cells. Our results elucidate the molecular mechanism of flavonoids acting on MIF and shed light on developing lead compounds against MIF-involved diseases.

Identification and Structure-Activity Relationships of Dietary Flavonoids as Human Macrophage Migration Inhibitory Factor (MIF) Inhibitors.,Yang L, Guo D, Fan C J Agric Food Chem. 2021 Sep 8;69(35):10138-10150. doi: 10.1021/acs.jafc.1c03367. , Epub 2021 Aug 30. PMID:34459191<ref>PMID:34459191</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7e45" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fan CP]]
[[Category: Yang L]]