6peg - Revision history

OCA at 07:27, 11 October 2023

OCA — Wed, 11 Oct 2023 07:27:47 GMT

←Older revision		Revision as of 07:27, 11 October 2023
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	<StructureSection load='6peg' size='340' side='right'caption='[[6peg]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6peg' size='340' side='right'caption='[[6peg]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6peg]] 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=6PEG OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6PEG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6peg]] 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=6PEG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PEG FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4FQ:4-amino-5-hydroxy-6-[(E)-(3-{[3-(2-methylpropanoyl)pyrazolo[1,5-a]pyridin-2-yl]methyl}phenyl)diazenyl]naphthalene-1,3-disulfonic+acid'>4FQ</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4FQ:4-amino-5-hydroxy-6-[(E)-(3-{[3-(2-methylpropanoyl)pyrazolo[1,5-a]pyridin-2-yl]methyl}phenyl)diazenyl]naphthalene-1,3-disulfonic+acid'>4FQ</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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~~://proteopedia.org/fgij/fg.htm?mol=6peg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6peg OCA], [~~http~~://pdbe.org/6peg PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6peg RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6peg PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6peg 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=6peg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6peg OCA], [https://pdbe.org/6peg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6peg RCSB], [https://www.ebi.ac.uk/pdbsum/6peg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6peg 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 ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Asojo~~, O A]]~~	+	[[Category: Asojo OA]]
-	~~[[Category: Drug discovery]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Isomerase]]~~	+
-	~~[[Category: Mif~~]]	+

OCA at 07:32, 4 November 2020

OCA — Wed, 04 Nov 2020 07:32:14 GMT

←Older revision		Revision as of 07:32, 4 November 2020
Line 3:		Line 3:
	<StructureSection load='6peg' size='340' side='right'caption='[[6peg]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6peg' size='340' side='right'caption='[[6peg]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6peg]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PEG OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6PEG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6peg]] 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=6PEG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PEG FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4FQ:4-amino-5-hydroxy-6-[(E)-(3-{[3-(2-methylpropanoyl)pyrazolo[1,5-a]pyridin-2-yl]methyl}phenyl)diazenyl]naphthalene-1,3-disulfonic+acid'>4FQ</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <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=4FQ:4-amino-5-hydroxy-6-[(E)-(3-{[3-(2-methylpropanoyl)pyrazolo[1,5-a]pyridin-2-yl]methyl}phenyl)diazenyl]naphthalene-1,3-disulfonic+acid'>4FQ</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=6peg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6peg OCA], [http://pdbe.org/6peg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6peg RCSB], [http://www.ebi.ac.uk/pdbsum/6peg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6peg 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://proteopedia.org/fgij/fg.htm?mol=6peg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6peg OCA], [http://pdbe.org/6peg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6peg RCSB], [http://www.ebi.ac.uk/pdbsum/6peg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6peg ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 11:		Line 12:
	== 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 ==
		+	Human Macrophage Migration Inhibitory Factor (MIF) is a trimeric cytokine implicated in a number of inflammatory and autoimmune diseases and cancer. We previously reported that the dye p425 (Chicago Sky Blue), which bound MIF at the interface of two MIF trimers covering the tautomerase and allosteric pockets, revealed a unique strategy to block MIF's pro-inflammatory activities. Structural liabilities, including the large size, precluded p425 as a medicinal chemistry lead for drug development. We report here a rational design strategy linking only the fragment of p425 that binds over the tautomerase pocket to the core of ibudilast, a known MIF allosteric site-specific inhibitor. The chimeric compound, termed L2-4048, was shown by X-ray crystallography to bind at the allosteric and tautomerase sites as anticipated. L2-4048 retained target binding and blocked MIF's tautomerase CD74 receptor binding, and pro-inflammatory activities. Our studies lay the foundation for the design and synthesis of smaller and more drug-like compounds that retain the MIF inhibitory properties of this chimera.
		+
		+	Inhibition of Macrophage Migration Inhibitory Factor by a Chimera of Two Allosteric Binders.,Cirillo PF, Asojo OA, Khire U, Lee Y, Mootien S, Hegan P, Sutherland AG, Peterson-Roth E, Ledizet M, Koski RA, Anthony KG ACS Med Chem Lett. 2019 Nov 19;11(10):1843-1847. doi:, 10.1021/acsmedchemlett.9b00351. eCollection 2020 Oct 8. PMID:33062162<ref>PMID:33062162</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6peg" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Macrophage inhibitory factor 3D structures\|Macrophage inhibitory factor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Asojo, O A]]		[[Category: Asojo, O A]]

OCA at 06:52, 27 November 2019

OCA — Wed, 27 Nov 2019 06:52:10 GMT

←Older revision		Revision as of 06:52, 27 November 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6peg is ~~ON HOLD until Paper Publication~~	+	==MIF with a allosteric inhibitor==
-		+	<StructureSection load='6peg' size='340' side='right'caption='[[6peg]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6peg]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PEG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PEG FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4FQ:4-amino-5-hydroxy-6-[(E)-(3-{[3-(2-methylpropanoyl)pyrazolo[1,5-a]pyridin-2-yl]methyl}phenyl)diazenyl]naphthalene-1,3-disulfonic+acid'>4FQ</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<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=6peg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6peg OCA], [http://pdbe.org/6peg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6peg RCSB], [http://www.ebi.ac.uk/pdbsum/6peg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6peg 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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Asojo, O A]]
		+	[[Category: Drug discovery]]
		+	[[Category: Inhibitor]]
		+	[[Category: Isomerase]]
		+	[[Category: Mif]]

OCA at 07:11, 2 October 2019

OCA — Wed, 02 Oct 2019 07:11:03 GMT

←Older revision		Revision as of 07:11, 2 October 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6peg is ON HOLD	+	The entry 6peg is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6peg" [edit=sysop:move=sysop]

OCA — Wed, 26 Jun 2019 05:21:35 GMT

Protected "6peg" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:21, 26 June 2019

OCA: New page: '''Unreleased structure''' The entry 6peg is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 26 Jun 2019 05:21:34 GMT

New page: '''Unreleased structure''' The entry 6peg is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6peg is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]