4eui - Revision history

OCA at 15:09, 14 March 2024

2024-03-14T15:09:28Z

←Older revision		Revision as of 15:09, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4eui]] 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=4EUI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EUI FirstGlance]. <br>		<table><tr><td colspan='2'>[[4eui]] 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=4EUI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EUI FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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]] 1.7Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=4eui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eui OCA], [https://pdbe.org/4eui PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eui RCSB], [https://www.ebi.ac.uk/pdbsum/4eui PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eui ProSAT]</span></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=4eui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eui OCA], [https://pdbe.org/4eui PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eui RCSB], [https://www.ebi.ac.uk/pdbsum/4eui PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eui ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== Function ==		== 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>		[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 key mediator of inflammatory responses and innate immunity and has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. The oligomerization of MIF, more specifically trimer formation, is essential for its keto-enol tautomerase activity and probably mediates several of its interactions and biological activities, including its binding to its receptor CD74 and activation of certain signaling pathways. Therefore, understanding the molecular factors governing the oligomerization of MIF and the role of quaternary structure in modulating its structural stability and multifunctional properties is crucial for understanding the function of MIF in health and disease. Herein, we describe highly conserved intersubunit interactions involving the hydrophobic packing of the side chain of Leu46 onto the beta-strand beta3 of one monomer within a hydrophobic pocket from the adjacent monomer constituted by residues Arg11, Val14, Phe18, Leu19, Val39, His40, Val41, Val42, and Pro43. To elucidate the structural significance of these intersubunit interactions and their relative contribution to MIF's trimerization, structural stability and catalytic activity, we generated three point mutations where Leu46 was replaced by glycine (L46G), alanine (L46A) and phenylalanine (L46F), and their structural properties, stability, oligomerization state, and catalytic activity were characterized using a battery of biophysical methods and X-ray crystallography. Our findings provide new insights into the role of the Leu46 hydrophobic pocket in stabilizing the conformational state of MIF in solution. Disrupting the Leu46 hydrophobic interaction perturbs the secondary and tertiary structure of the protein but has no effect on its oligomerization state.
-
-	Characterization of molecular determinants of the conformational stability of macrophage migration inhibitory factor: leucine 46 hydrophobic pocket.,El-Turk F, Fauvet B, Ashrafi A, Ouertatani-Sakouhi H, Cho MK, Neri M, Cascella M, Rothlisberger U, Pojer F, Zweckstetter M, Lashuel H PLoS One. 2012;7(9):e45024. doi: 10.1371/journal.pone.0045024. Epub 2012 Sep 21. PMID:23028743<ref>PMID:23028743</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4eui" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 04:17, 7 October 2022

2022-10-07T04:17:13Z

←Older revision		Revision as of 04:17, 7 October 2022
Line 1:		Line 1:

	==Crystal Structure of MIF L46F mutant==		==Crystal Structure of MIF L46F mutant==
-	<StructureSection load='4eui' size='340' side='right' caption='[[4eui]], [[Resolution\|resolution]] 1.70Å' scene=''>	+	<StructureSection load='4eui' size='340' side='right'caption='[[4eui]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4eui]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EUI OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4EUI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4eui]] 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=4EUI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EUI FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4etg\|4etg]], [[4evg\|4evg]]</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=4eui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eui OCA], [https://pdbe.org/4eui PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eui RCSB], [https://www.ebi.ac.uk/pdbsum/4eui PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eui ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MIF, GLIF, MMIF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=4eui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eui OCA], [~~http~~://pdbe.org/4eui PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4eui RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4eui PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4eui ProSAT]</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 24:		Line 22:

	==See Also==		==See Also==
-	*[[Macrophage inhibitory factor\|Macrophage inhibitory factor]]	+	*[[Macrophage inhibitory factor 3D structures\|Macrophage inhibitory factor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Ashrafi, A~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Lashuel, H~~]]	+	[[Category: Ashrafi A]]
-	[[Category: ~~Pojer, F~~]]	+	[[Category: Lashuel H]]
-	[[Category: ~~Isomerase]]~~	+	[[Category: Pojer F]]
-	~~[[Category: Keto-enol tautomerase~~]]	+

OCA at 17:36, 4 August 2016

2016-08-04T17:36:07Z

←Older revision		Revision as of 17:36, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of MIF L46F mutant==		==Crystal Structure of MIF L46F mutant==
	<StructureSection load='4eui' size='340' side='right' caption='[[4eui]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='4eui' size='340' side='right' caption='[[4eui]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4eui]] 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=4EUI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EUI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4eui]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EUI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EUI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4etg\|4etg]], [[4evg\|4evg]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4etg\|4etg]], [[4evg\|4evg]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MIF, GLIF, MMIF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MIF, GLIF, MMIF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4eui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eui OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eui RCSB], [http://www.ebi.ac.uk/pdbsum/4eui PDBsum]</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=4eui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eui OCA], [http://pdbe.org/4eui PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4eui RCSB], [http://www.ebi.ac.uk/pdbsum/4eui PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4eui ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	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 4eui" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 27:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Ashrafi, A]]		[[Category: Ashrafi, A]]
	[[Category: Lashuel, H]]		[[Category: Lashuel, H]]

OCA at 11:30, 21 December 2014

2014-12-21T11:30:46Z

←Older revision		Revision as of 11:30, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4eui~~\| ~~PDB~~=4eui \| ~~SCENE~~= }}	+	==Crystal Structure of MIF L46F mutant==
-	===~~Crystal Structure of~~ MIF ~~L46F mutant~~===	+	<StructureSection load='4eui' size='340' side='right' caption='[[4eui]], [[Resolution\|resolution]] 1.70Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23028743}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4eui]] 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=4EUI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EUI FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4etg\|4etg]], [[4evg\|4evg]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MIF, GLIF, 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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eui OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eui RCSB], [http://www.ebi.ac.uk/pdbsum/4eui PDBsum]</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.		[[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 ==
-	==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>		[[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 key mediator of inflammatory responses and innate immunity and has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. The oligomerization of MIF, more specifically trimer formation, is essential for its keto-enol tautomerase activity and probably mediates several of its interactions and biological activities, including its binding to its receptor CD74 and activation of certain signaling pathways. Therefore, understanding the molecular factors governing the oligomerization of MIF and the role of quaternary structure in modulating its structural stability and multifunctional properties is crucial for understanding the function of MIF in health and disease. Herein, we describe highly conserved intersubunit interactions involving the hydrophobic packing of the side chain of Leu46 onto the beta-strand beta3 of one monomer within a hydrophobic pocket from the adjacent monomer constituted by residues Arg11, Val14, Phe18, Leu19, Val39, His40, Val41, Val42, and Pro43. To elucidate the structural significance of these intersubunit interactions and their relative contribution to MIF's trimerization, structural stability and catalytic activity, we generated three point mutations where Leu46 was replaced by glycine (L46G), alanine (L46A) and phenylalanine (L46F), and their structural properties, stability, oligomerization state, and catalytic activity were characterized using a battery of biophysical methods and X-ray crystallography. Our findings provide new insights into the role of the Leu46 hydrophobic pocket in stabilizing the conformational state of MIF in solution. Disrupting the Leu46 hydrophobic interaction perturbs the secondary and tertiary structure of the protein but has no effect on its oligomerization state.

-	~~==About this Structure==~~	+	Characterization of molecular determinants of the conformational stability of macrophage migration inhibitory factor: leucine 46 hydrophobic pocket.,El-Turk F, Fauvet B, Ashrafi A, Ouertatani-Sakouhi H, Cho MK, Neri M, Cascella M, Rothlisberger U, Pojer F, Zweckstetter M, Lashuel H PLoS One. 2012;7(9):e45024. doi: 10.1371/journal.pone.0045024. Epub 2012 Sep 21. PMID:23028743<ref>PMID:23028743</ref>
-	~~[[4eui]] 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=4EUI OCA]~~.	+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

	==See Also==		==See Also==
	*[[Macrophage inhibitory factor\|Macrophage inhibitory factor]]		*[[Macrophage inhibitory factor\|Macrophage inhibitory factor]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:023028743</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Ashrafi, A.]]	+	[[Category: Ashrafi, A]]
-	[[Category: Lashuel, H.]]	+	[[Category: Lashuel, H]]
-	[[Category: Pojer, F.]]	+	[[Category: Pojer, F]]
	[[Category: Isomerase]]		[[Category: Isomerase]]
	[[Category: Keto-enol tautomerase]]		[[Category: Keto-enol tautomerase]]

OCA at 11:17, 24 July 2013

2013-07-24T11:17:16Z

←Older revision		Revision as of 11:17, 24 July 2013
Line 1:		Line 1:
	{{STRUCTURE_4eui\| PDB=4eui \| SCENE= }}		{{STRUCTURE_4eui\| PDB=4eui \| SCENE= }}
	===Crystal Structure of MIF L46F mutant===		===Crystal Structure of MIF L46F mutant===
		+	{{ABSTRACT_PUBMED_23028743}}

	==Disease==		==Disease==
Line 6:		Line 7:

	==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>	+	[[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>

	==About this Structure==		==About this Structure==
	[[4eui]] 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=4EUI OCA].		[[4eui]] 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=4EUI OCA].
		+
		+	==See Also==
		+	*[[Macrophage inhibitory factor\|Macrophage inhibitory factor]]

	==Reference==		==Reference==
-	<references group="xtra"/><references/>	+	<ref group="xtra">PMID:023028743</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Ashrafi, A.]]		[[Category: Ashrafi, A.]]

OCA at 23:23, 24 March 2013

2013-03-24T23:23:35Z

←Older revision		Revision as of 23:23, 24 March 2013
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-	[[Image:4eui.jpg\|left\|200px]]
-
	{{STRUCTURE_4eui\| PDB=4eui \| SCENE= }}		{{STRUCTURE_4eui\| PDB=4eui \| SCENE= }}
-
	===Crystal Structure of MIF L46F mutant===		===Crystal Structure of MIF L46F mutant===

		+	==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>

	==About this Structure==		==About this Structure==
	[[4eui]] 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=4EUI OCA].		[[4eui]] 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=4EUI OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Ashrafi, A.]]		[[Category: Ashrafi, A.]]

OCA at 06:25, 3 October 2012

2012-10-03T06:25:20Z

←Older revision		Revision as of 06:25, 3 October 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4eui.jpg\|left\|200px]]

-	~~The entry~~ 4eui ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4eui\| PDB=4eui \| SCENE= }}

-	~~Authors: Ashrafi, A., Pojer, F., Lashuel, H.~~	+	===Crystal Structure of MIF L46F mutant===

-	~~Description: Crystal~~ Structure ~~of MIF L46F mutant~~	+
		+	==About this Structure==
		+	[[4eui]] 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=4EUI OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Ashrafi, A.]]
		+	[[Category: Lashuel, H.]]
		+	[[Category: Pojer, F.]]
		+	[[Category: Isomerase]]
		+	[[Category: Keto-enol tautomerase]]

OCA at 08:50, 16 May 2012

2012-05-16T08:50:39Z

←Older revision		Revision as of 08:50, 16 May 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4eui is ON HOLD	+	The entry 4eui is ON HOLD until Paper Publication

	Authors: Ashrafi, A., Pojer, F., Lashuel, H.		Authors: Ashrafi, A., Pojer, F., Lashuel, H.

	Description: Crystal Structure of MIF L46F mutant		Description: Crystal Structure of MIF L46F mutant

OCA: Protected "4eui" [edit=sysop:move=sysop]

2012-05-02T19:00:00Z

Protected "4eui" [edit=sysop:move=sysop]

←Older revision

Revision as of 19:00, 2 May 2012

OCA: New page: '''Unreleased structure''' The entry 4eui is ON HOLD Authors: Ashrafi, A., Pojer, F., Lashuel, H. Description: Crystal Structure of MIF L46F mutant

2012-05-02T18:59:59Z

New page: '''Unreleased structure''' The entry 4eui is ON HOLD Authors: Ashrafi, A., Pojer, F., Lashuel, H. Description: Crystal Structure of MIF L46F mutant

New page

'''Unreleased structure'''

The entry 4eui is ON HOLD

Authors: Ashrafi, A., Pojer, F., Lashuel, H.

Description: Crystal Structure of MIF L46F mutant