6peg

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 3: Line 3:
<StructureSection load='6peg' size='340' side='right'caption='[[6peg]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
<StructureSection load='6peg' size='340' side='right'caption='[[6peg]], [[Resolution|resolution]] 2.00&Aring;' 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&reg;/PubMed&reg;, 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]]

Revision as of 07:32, 4 November 2020

MIF with a allosteric inhibitor

PDB ID 6peg

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6peg"
Personal tools