|
|
| (3 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Macrophage Migration Inhibitory Factor (MIF) with Covalently Bound L-sulforaphane== | | ==Macrophage Migration Inhibitory Factor (MIF) with Covalently Bound L-sulforaphane== |
| - | <StructureSection load='3smc' size='340' side='right' caption='[[3smc]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='3smc' size='340' side='right'caption='[[3smc]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3smc]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SMC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SMC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3smc]] 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=3SMC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SMC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=LE3:N-{4-[(R)-METHYLSULFINYL]BUTYL}THIOFORMAMIDE'>LE3</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3smb|3smb]]</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=LE3:N-{4-[(R)-METHYLSULFINYL]BUTYL}THIOFORMAMIDE'>LE3</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLIF, MIF, MMIF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3smc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3smc OCA], [https://pdbe.org/3smc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3smc RCSB], [https://www.ebi.ac.uk/pdbsum/3smc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3smc ProSAT]</span></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=3smc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3smc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3smc RCSB], [http://www.ebi.ac.uk/pdbsum/3smc PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == 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. | + | [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 == | | == 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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 20: |
Line 20: |
| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3smc" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Macrophage inhibitory factor|Macrophage inhibitory factor]] | + | *[[Macrophage inhibitory factor 3D structures|Macrophage inhibitory factor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 28: |
Line 29: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Crichlow, G V]] | + | [[Category: Large Structures]] |
| - | [[Category: Lolis, E J]] | + | [[Category: Crichlow GV]] |
| - | [[Category: Cytokine]] | + | [[Category: Lolis EJ]] |
| - | [[Category: Isomerase-isomerase inhibitor complex]]
| + | |
| - | [[Category: Receptor binding]]
| + | |
| - | [[Category: Secreted]]
| + | |
| Structural highlights
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
Regulation of cellular processes by dietary nutrients is known to affect the likelihood of cancer development. One class of cancer-preventive nutrients, isothiocyanates (ITCs), derived from the consumption of cruciferous vegetables, is known to have various effects on cellular biochemistry. One target of ITCs is macrophage migration inhibitory factor (MIF), a widely expressed protein with known inflammatory, pro-tumorigenic, pro-angiogenic, and anti-apoptotic properties. MIF is covalently inhibited by a variety of ITCs, which in part may explain how they exert their cancer-preventive effects. We report the crystallographic structures of human MIF bound to phenethylisothiocyanate and to l-sulforaphane (dietary isothiocyanates derived from watercress and broccoli, respectively) and correlate structural features of these two isothiocyanates with their second-order rate constants for MIF inactivation. We also characterize changes in the MIF structure using nuclear magnetic resonance heteronuclear single-quantum coherence spectra of these complexes and observe many changes at the subunit interface. While a number of chemical shifts do not change, many of those that change do not have features similar in magnitude or direction for the two isothiocyanates. The difference in the binding modes of these two ITCs provides a means of using structure-activity relationships to reveal insights into MIF biological interactions. The results of this study provide a framework for the development of therapeutics that target MIF.
Structural Interactions Dictate the Kinetics of Macrophage Migration Inhibitory Factor Inhibition by Different Cancer-Preventive Isothiocyanates.,Crichlow GV, Fan C, Keeler C, Hodsdon M, Lolis EJ Biochemistry. 2012 Sep 11. PMID:22931430[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Crichlow GV, Fan C, Keeler C, Hodsdon M, Lolis EJ. Structural Interactions Dictate the Kinetics of Macrophage Migration Inhibitory Factor Inhibition by Different Cancer-Preventive Isothiocyanates. Biochemistry. 2012 Sep 11. PMID:22931430 doi:http://dx.doi.org/10.1021/bi3005494
|
