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4gai

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Revision as of 06:45, 26 October 2022

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

Structural highlights

4gai is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1]

Publication Abstract from PubMed

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.

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Van Damme J, De Ley M, Opdenakker G, Billiau A, De Somer P, Van Beeumen J. Homogeneous interferon-inducing 22K factor is related to endogenous pyrogen and interleukin-1. Nature. 1985 Mar 21-27;314(6008):266-8. PMID:3920526
↑ 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. Design of a superior cytokine antagonist for topical ophthalmic use. 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 doi:http://dx.doi.org/10.1073/pnas.1217996110

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4gai"

@@ Line 3: / Line 3: @@
 <StructureSection load='4gai' size='340' side='right'caption='[[4gai]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
 == Structural highlights ==
-<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>
+<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>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gaf|4gaf]]</td></tr>
+</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=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>
-<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>
 </table>
+== Function ==
+[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 21: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Barnes, T M]]
+[[Category: Barnes TM]]
-[[Category: Furfine, E S]]
+[[Category: Furfine ES]]
-[[Category: Garcia, K C]]
+[[Category: Garcia KC]]
-[[Category: Hou, J]]
+[[Category: Hou J]]
-[[Category: Kiner, O]]
+[[Category: Kiner O]]
-[[Category: King, B]]
+[[Category: King B]]
-[[Category: Kovalchin, J T]]
+[[Category: Kovalchin JT]]
-[[Category: Masci, A]]
+[[Category: Masci A]]
-[[Category: Shu, Y]]
+[[Category: Shu Y]]
-[[Category: Thomas, C]]
+[[Category: Thomas C]]
-[[Category: Townson, S A]]
+[[Category: Townson SA]]
-[[Category: Beta-trefoil]]
-[[Category: Il-1 signaling]]
-[[Category: Il-1beta]]
-[[Category: Il-1r1]]
-[[Category: Il-1ra]]
-[[Category: Signaling protein]]

4gai

From Proteopedia

Revision as of 06:45, 26 October 2022

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

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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