6cbh: Difference between revisions

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-'''Unreleased structure'''
-The entry 6cbh is ON HOLD
+==Macrophage Migration Inhibitory Factor in Complex with a Pyrazole Inhibitor (8m)==
+<StructureSection load='6cbh' size='340' side='right' caption='[[6cbh]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6cbh]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CBH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CBH FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EWJ:5-(3-fluoro-1H-pyrazol-4-yl)-2-[(naphthalen-2-yl)oxy]benzoic+acid'>EWJ</scene>, <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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6cbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cbh OCA], [http://pdbe.org/6cbh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cbh RCSB], [http://www.ebi.ac.uk/pdbsum/6cbh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cbh ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/MIF_HUMAN MIF_HUMAN]] Genetic variations in MIF are associated with susceptibility to rheumatoid arthritis systemic juvenile (RASJ) [MIM:[http://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 ==
+[[http://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 a proinflammatory cytokine that is implicated in the regulation of inflammation, cell proliferation, and neurological disorders. MIF is also an enzyme that functions as a keto-enol tautomerase. Most potent MIF tautomerase inhibitors incorporate a phenol, which hydrogen bonds to Asn97 in the active site. Starting from a 113-muM docking hit, we report results of structure-based and computer-aided design that have provided substituted pyrazoles as phenol alternatives with potencies of 60-70 nM. Crystal structures of complexes of MIF with the pyrazoles highlight the contributions of hydrogen bonding with Lys32 and Asn97, and aryl-aryl interactions with Tyr36, Tyr95, and Phe113 to the binding.
-Authors: Robertson, M.J., Krimmer, S.G., Jorgensen, W.L.
+Optimization of Pyrazoles as Phenol Surrogates to Yield Potent Inhibitors of Macrophage Migration Inhibitory Factor.,Trivedi-Parmar V, Robertson MJ, Cisneros JA, Krimmer SG, Jorgensen WL ChemMedChem. 2018 Mar 25. doi: 10.1002/cmdc.201800158. PMID:29575754<ref>PMID:29575754</ref>
-Description: Macrophage Migration Inhibitory Factor in Complex with a Pyrazole Inhibitor (8m)
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Krimmer, S.G]]
+<div class="pdbe-citations 6cbh" style="background-color:#fffaf0;"></div>
-[[Category: Robertson, M.J]]
+== References ==
-[[Category: Jorgensen, W.L]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Jorgensen, W L]]
+[[Category: Krimmer, S G]]
+[[Category: Robertson, M J]]
+[[Category: Complex]]
+[[Category: Cytokine]]
+[[Category: Inhibitor]]