4f2k: Difference between revisions
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== | ==Macrophage Migration Inhibitory Factor covalently complexed with phenethylisothiocyanate== | ||
[[http://www.uniprot.org/uniprot/MIF_HUMAN MIF_HUMAN | <StructureSection load='4f2k' size='340' side='right'caption='[[4f2k]], [[Resolution|resolution]] 1.53Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4f2k]] 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=4F2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F2K 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]] 1.53Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=LE2:N-(2-PHENYLETHYL)THIOFORMAMIDE'>LE2</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=4f2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f2k OCA], [https://pdbe.org/4f2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f2k RCSB], [https://www.ebi.ac.uk/pdbsum/4f2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f2k 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 == | |||
Macrophage migration inhibitory factor is irreversibly inhibited via covalent modification by phenethyl isothiocyanate, a naturally occurring compound with anti-inflammatory and anticancer properties. The structure of the modified protein obtained from X-ray diffraction data to 1.64 A resolution is presented. The inhibitor sits within a deep hydrophobic pocket between subunits of the homotrimer and is highly ordered. The secondary structure of macrophage migratory inhibitory factor is unchanged by this modification, but there are significant rearrangements, including of the side-chain position of Tyr37 and the main chain of residues 31-34. These changes may explain the decreased binding of the modified protein to the receptor CD74. Together with the pocket, the areas of conformational change define specific targets for the design of more selective and potent inhibitors as potential therapeutics. | |||
Macrophage migration inhibitory factor covalently complexed with phenethyl isothiocyanate.,Tyndall JD, Lue H, Rutledge MT, Bernhagen J, Hampton MB, Wilbanks SM Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Sep 1;68(Pt 9):999-1002., doi: 10.1107/S1744309112030552. Epub 2012 Aug 29. PMID:22949182<ref>PMID:22949182</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4f2k" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
<references | *[[Macrophage inhibitory factor 3D structures|Macrophage inhibitory factor 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Bernhagen J]] | ||
[[Category: Hampton MB]] | |||
[[Category: Rutledge MT]] | |||
[[Category: | [[Category: Tyndall JDA]] | ||
[[Category: | [[Category: Wilbanks SM]] | ||
[[Category: | |||
[[Category: | |||
Latest revision as of 16:50, 8 November 2023
Macrophage Migration Inhibitory Factor covalently complexed with phenethylisothiocyanateMacrophage Migration Inhibitory Factor covalently complexed with phenethylisothiocyanate
Structural highlights
DiseaseMIF_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. FunctionMIF_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 PubMedMacrophage migration inhibitory factor is irreversibly inhibited via covalent modification by phenethyl isothiocyanate, a naturally occurring compound with anti-inflammatory and anticancer properties. The structure of the modified protein obtained from X-ray diffraction data to 1.64 A resolution is presented. The inhibitor sits within a deep hydrophobic pocket between subunits of the homotrimer and is highly ordered. The secondary structure of macrophage migratory inhibitory factor is unchanged by this modification, but there are significant rearrangements, including of the side-chain position of Tyr37 and the main chain of residues 31-34. These changes may explain the decreased binding of the modified protein to the receptor CD74. Together with the pocket, the areas of conformational change define specific targets for the design of more selective and potent inhibitors as potential therapeutics. Macrophage migration inhibitory factor covalently complexed with phenethyl isothiocyanate.,Tyndall JD, Lue H, Rutledge MT, Bernhagen J, Hampton MB, Wilbanks SM Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Sep 1;68(Pt 9):999-1002., doi: 10.1107/S1744309112030552. Epub 2012 Aug 29. PMID:22949182[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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