5bvp: Difference between revisions

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-'''Unreleased structure'''
+==The molecular mode of action and species specificity of canakinumab, a human monoclonal antibody neutralizing IL-1beta==
+<StructureSection load='5bvp' size='340' side='right' caption='[[5bvp]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5bvp]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BVP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BVP FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
+<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=5bvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bvp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5bvp RCSB], [http://www.ebi.ac.uk/pdbsum/5bvp PDBsum]</span></td></tr>
+</table>
+== Function ==
+[[http://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 ==
+Interleukin-1beta (IL-1beta) plays a key role in autoinflammatory diseases, such as systemic juvenile idiopathic arthritis (sJIA) or cryopyrin-associated periodic syndrome (CAPS). Canakinumab, a human monoclonal anti-IL-1beta antibody, was recently approved for human use under the brand name Ilaris(R). Canakinumab does not cross-react with IL-1beta from mouse, rat, rabbit, or macaques. The crystal structure of the canakinumab Fab bound to human IL-1beta was determined in an attempt to rationalize the species specificity. The X-ray analysis reveals a complex surface epitope with an intricate network of well-ordered water molecules at the antibody-antigen interface. The canakinumab paratope is largely pre-organized, as demonstrated by the structure determination of the free Fab. Glu 64 of human IL-1beta is a pivotal epitope residue explaining the exquisite species specificity of canakinumab. We identified marmoset as the only non-human primate species that carries Glu 64 in its IL-1beta and demonstrates full cross-reactivity of canakinumab, thereby enabling toxicological studies in this species. As demonstrated by the X-ray structure of the complex with IL-1beta, canakinumab binds IL-1beta on the opposite side with respect to the IL-1RAcP binding site, and in an approximately orthogonal orientation with respect to IL-1RI. However, the antibody and IL-1RI binding sites slightly overlap and the VH region of canakinumab would sterically interfere with the D1 domain of IL-1RI, as shown by a structural overlay with the IL-1beta:IL-1RI complex. Therefore, direct competition with IL-1RI for IL-1beta binding is the molecular mechanism of neutralization by canakinumab, which is also confirmed by competition assays with recombinant IL-1RI and IL-1RII.
-The entry 5bvp is ON HOLD  until Paper Publication
+The molecular mode of action and species specificity of canakinumab, a human monoclonal antibody neutralizing IL-1beta.,Rondeau JM, Ramage P, Zurini M, Gram H MAbs. 2015 Aug 18:0. PMID:26284424<ref>PMID:26284424</ref>
-Authors: Rondeau, J.M.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: The molecular mode of action and species specificity of canakinumab, a human monoclonal antibody neutralizing IL-1beta
+== References ==
-[[Category: Unreleased Structures]]
+<references/>
-[[Category: Rondeau, J.M]]
+__TOC__
+</StructureSection>
+[[Category: Rondeau, J M]]
+[[Category: Beta trefoil]]
+[[Category: Cytokine]]
+[[Category: Fab]]
+[[Category: Immune system]]
+[[Category: Immunoglobulin]]