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4gai

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<StructureSection load='4gai' size='340' side='right'caption='[[4gai]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
<StructureSection load='4gai' size='340' side='right'caption='[[4gai]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4gai]] is a 2 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=4GAI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GAI FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4gai]] is a 2 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=4GAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GAI FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gaf|4gaf]]</td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.49&#8491;</td></tr>
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<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=4gai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gai OCA], [http://pdbe.org/4gai PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gai RCSB], [http://www.ebi.ac.uk/pdbsum/4gai PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gai ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4gai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gai OCA], [https://pdbe.org/4gai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gai RCSB], [https://www.ebi.ac.uk/pdbsum/4gai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gai ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/IL1B_HUMAN IL1B_HUMAN] Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.<ref>PMID:3920526</ref>
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IL-1 is a key inflammatory and immune mediator in many diseases, including dry-eye disease, and its inhibition is clinically efficacious in rheumatoid arthritis and cryopyrin-associated periodic syndromes. To treat ocular surface disease with a topical biotherapeutic, the uniqueness of the site necessitates consideration of the agent's size, target location, binding kinetics, and thermal stability. Here we chimerized two IL-1 receptor ligands, IL-1beta and IL-1Ra, to create an optimized receptor antagonist, EBI-005, for topical ocular administration. EBI-005 binds its target, IL-1R1, 85-fold more tightly than IL-1Ra, and this increase translates to an approximately 100-fold increase in potency in vivo. EBI-005 preserves the affinity bias of IL-1Ra for IL-1R1 over the decoy receptor (IL-1R2), and, surprisingly, is also more thermally stable than either parental molecule. This rationally designed antagonist represents a unique approach to therapeutic design that can potentially be exploited for other beta-trefoil family proteins in the IL-1 and FGF families.
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Design of a superior cytokine antagonist for topical ophthalmic use.,Hou J, Townson SA, Kovalchin JT, Masci A, Kiner O, Shu Y, King BM, Schirmer E, Golden K, Thomas C, Garcia KC, Zarbis-Papastoitsis G, Furfine ES, Barnes TM Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3913-8. doi:, 10.1073/pnas.1217996110. Epub 2013 Feb 19. PMID:23431173<ref>PMID:23431173</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4gai" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Barnes, T M]]
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[[Category: Barnes TM]]
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[[Category: Furfine, E S]]
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[[Category: Furfine ES]]
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[[Category: Garcia, K C]]
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[[Category: Garcia KC]]
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[[Category: Hou, J]]
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[[Category: Hou J]]
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[[Category: Kiner, O]]
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[[Category: Kiner O]]
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[[Category: King, B]]
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[[Category: King B]]
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[[Category: Kovalchin, J T]]
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[[Category: Kovalchin JT]]
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[[Category: Masci, A]]
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[[Category: Masci A]]
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[[Category: Shu, Y]]
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[[Category: Shu Y]]
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[[Category: Thomas, C]]
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[[Category: Thomas C]]
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[[Category: Townson, S A]]
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[[Category: Townson SA]]
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[[Category: Beta-trefoil]]
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[[Category: Il-1 signaling]]
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[[Category: Il-1beta]]
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[[Category: Il-1r1]]
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[[Category: Il-1ra]]
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[[Category: Signaling protein]]
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Current revision

Crystal structure of EBI-005, a chimera of human IL-1beta and IL-1Ra

PDB ID 4gai

Drag the structure with the mouse to rotate

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