View source for 9bnq


==N-(4-(isothiocyanatomethyl)phenyl)methanesulfonamide complexed with Macrophage Migration Inhibitory Factor==
<StructureSection load='9bnq' size='340' side='right'caption='[[9bnq]], [[Resolution|resolution]] 1.09&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9bnq]] 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=9BNQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BNQ 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]] 1.09&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AQU:N-{[4-(methanesulfonamido)phenyl]methyl}methanethioamide'>A1AQU</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'>[https://proteopedia.org/fgij/fg.htm?mol=9bnq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bnq OCA], [https://pdbe.org/9bnq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bnq RCSB], [https://www.ebi.ac.uk/pdbsum/9bnq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bnq 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 (MIF) is a proinflammatory cytokine with roles in innate and adaptive human immune responses, as well as inflammation. MIF exerts its biological activity by binding to the cell surface receptor CD74 as well as intracellular signalling proteins. MIF also possesses keto-enol tautomerase activity. Inhibition of the tautomerase activity has been associated with loss of biological activity of MIF and a potential anticancer target. Isothiocyanates (ITCs) are a class of compounds present in cruciferous vegetables that inhibit the MIF tautomerase activity via covalent modification of the N-terminal proline. A range of substituted ITCs featuring benzyl, phenethyl and phenyl propyl isothiocyanates were designed, synthesised and tested to determine any structure activity relationship for inhibiting MIF. Crystal structures of covalent compounds 8 and 9 in complex with rhMIF revealed key hydrogen bonding and edge-to-face pi stacking interactions. Compound 9 and 11 with sub micromolar activity were tested in the NCI60 cancer cell lines panel. Both compounds showed tissue-specific reduced growth in colon and renal cancer cell lines, while one of these showed potent, dose-dependent inhibition of growth against all seven colon cancer cell lines (GI50 &lt; 2.5 microM) and all eight renal cancer cell lines (GI50 &lt; 2.2 microM).

Covalent isothiocyanate inhibitors of macrophage migration inhibitory factor as potential colorectal cancer treatments.,Tyndall J, Putha L, Kok LK, Fellner M, Rutledge MT, Gamble AB, Wilbanks SM, Vernall AJ ChemMedChem. 2024 Jul 8:e202400394. doi: 10.1002/cmdc.202400394. PMID:38977403<ref>PMID:38977403</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9bnq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fellner M]]
[[Category: Gamble AB]]
[[Category: Kok LK]]
[[Category: Putha L]]
[[Category: Rutledge MT]]
[[Category: Tyndall JDA]]
[[Category: Vernall AJ]]
[[Category: Wilbanks SM]]