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7e4a

From Proteopedia

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Crystal structure of MIF bound to compound 13

Structural highlights

7e4a is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.475Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MIF_HUMAN Genetic variations in MIF are associated with susceptibility to rheumatoid arthritis systemic juvenile (RASJ) [MIM: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

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.^[1] ^[2]

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^[3]

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

References

↑ Oddo M, Calandra T, Bucala R, Meylan PR. Macrophage migration inhibitory factor reduces the growth of virulent Mycobacterium tuberculosis in human macrophages. Infect Immun. 2005 Jun;73(6):3783-6. PMID:15908412 doi:10.1128/IAI.73.6.3783-3786.2005
↑ Emonts M, Sweep FC, Grebenchtchikov N, Geurts-Moespot A, Knaup M, Chanson AL, Erard V, Renner P, Hermans PW, Hazelzet JA, Calandra T. Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis. Clin Infect Dis. 2007 May 15;44(10):1321-8. Epub 2007 Apr 5. PMID:17443469 doi:10.1086/514344
↑ Yang L, Guo D, Fan C. Identification and Structure-Activity Relationships of Dietary Flavonoids as Human Macrophage Migration Inhibitory Factor (MIF) Inhibitors. J Agric Food Chem. 2021 Sep 8;69(35):10138-10150. PMID:34459191 doi:10.1021/acs.jafc.1c03367

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7e4a"

Categories: Homo sapiens | Large Structures | Fa CP | Guo DY | Yang L

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[7e4a]] 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=7E4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E4A FirstGlance]. <br>
-</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=HWL:2-piperidin-1-ylethyl+3-methyl-4-oxidanylidene-2-phenyl-chromene-8-carboxylate'>HWL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.475&#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=HWL:2-piperidin-1-ylethyl+3-methyl-4-oxidanylidene-2-phenyl-chromene-8-carboxylate'>HWL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=7e4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e4a OCA], [https://pdbe.org/7e4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e4a RCSB], [https://www.ebi.ac.uk/pdbsum/7e4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e4a ProSAT]</span></td></tr>
 </table>

7e4a

From Proteopedia

Current revision

Crystal structure of MIF bound to compound 13

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

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