1ljt

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[[Image:1ljt.jpg|left|200px]]<br /><applet load="1ljt" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1ljt, resolution 2.&Aring;" />
 
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'''Crystal Structure of Macrophage Migration Inhibitory Factor complexed with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole-acetic acid methyl ester (ISO-1)'''<br />
 
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==Overview==
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==Crystal Structure of Macrophage Migration Inhibitory Factor complexed with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole-acetic acid methyl ester (ISO-1)==
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Macrophage migration inhibitory factor (MIF) is an immunoregulatory, protein that is a potential therapeutic target for a number of, inflammatory diseases. Evidence exists that an unexpected catalytic active, site of MIF may have a biological function. To gain further insight into, the role of the catalytic active site, a series of mutational, structural, and biological activity studies were performed. The insertion of an, alanine between Pro-1 and Met-2 (PAM) abolishes a non-physiological, catalytic activity, and this mutant is defective in the in vitro, glucocorticoid counter-regulatory activity of MIF. The crystal structure, of MIF complexed to (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole, acetic acid methyl ester (ISO-1), an inhibitor of MIF d-dopachrome, tautomerase activity, reveals that ISO-1 binds to the same position of the, active site as p-hydroxyphenylpyruvic acid, a substrate of MIF. ISO-1, inhibits several MIF biological activities, further establishing a role, for the catalytic active site of MIF.
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<StructureSection load='1ljt' size='340' side='right'caption='[[1ljt]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1ljt]] 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=1LJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LJT FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HDI:3-(4-HYDROXYPHENYL)-4,5-DIHYDRO-5-ISOXAZOLE-ACETIC+ACID+METHYL+ESTER'>HDI</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ljt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ljt OCA], [https://pdbe.org/1ljt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ljt RCSB], [https://www.ebi.ac.uk/pdbsum/1ljt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ljt ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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.
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lj/1ljt_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ljt ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases associated with this structure: Persistent Mullerian duct syndrome, type I OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600957 600957]], Rheumatoid arthritis, systemic juvenile, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=153620 153620]]
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*[[Macrophage inhibitory factor 3D structures|Macrophage inhibitory factor 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1LJT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=HDI:'>HDI</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LJT OCA].
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__TOC__
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</StructureSection>
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==Reference==
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The tautomerase active site of macrophage migration inhibitory factor is a potential target for discovery of novel anti-inflammatory agents., Lubetsky JB, Dios A, Han J, Aljabari B, Ruzsicska B, Mitchell R, Lolis E, Al-Abed Y, J Biol Chem. 2002 Jul 12;277(28):24976-82. Epub 2002 May 7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11997397 11997397]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Al-Abed, Y.]]
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[[Category: Al-Abed Y]]
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[[Category: Aljabari, B.]]
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[[Category: Aljabari B]]
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[[Category: Dios, A.]]
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[[Category: Dios A]]
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[[Category: Han, J.]]
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[[Category: Han J]]
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[[Category: Lolis, E.]]
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[[Category: Lolis E]]
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[[Category: Lubetsky, J.B.]]
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[[Category: Lubetsky JB]]
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[[Category: Mitchell, R.]]
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[[Category: Mitchell R]]
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[[Category: Ruzsicska, B.]]
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[[Category: Ruzsicska B]]
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[[Category: HDI]]
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[[Category: protein-inhibitor complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:18:50 2008''
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Current revision

Crystal Structure of Macrophage Migration Inhibitory Factor complexed with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole-acetic acid methyl ester (ISO-1)

PDB ID 1ljt

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