3nfs: Difference between revisions
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==Crystal structure the Fab fragment of therapeutic antibody daclizumab== | ==Crystal structure the Fab fragment of therapeutic antibody daclizumab== | ||
<StructureSection load='3nfs' size='340' side='right' caption='[[3nfs]], [[Resolution|resolution]] 2.60Å' scene=''> | <StructureSection load='3nfs' size='340' side='right' caption='[[3nfs]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3nfs]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3nfs]] 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=3NFS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NFS FirstGlance]. <br> | ||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3iu3|3iu3]], [[3nfp|3nfp]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3iu3|3iu3]], [[3nfp|3nfp]]</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=3nfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nfs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nfs RCSB], [http://www.ebi.ac.uk/pdbsum/3nfs PDBsum]</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=3nfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nfs OCA], [http://pdbe.org/3nfs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3nfs RCSB], [http://www.ebi.ac.uk/pdbsum/3nfs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3nfs ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3nfs ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3nfs" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[ | *[[3D structures of antibody|3D structures of antibody]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Human]] | ||
[[Category: Ding, J]] | [[Category: Ding, J]] | ||
[[Category: Du, J]] | [[Category: Du, J]] | ||
Revision as of 21:48, 4 August 2016
Crystal structure the Fab fragment of therapeutic antibody daclizumabCrystal structure the Fab fragment of therapeutic antibody daclizumab
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedInterleukin-2 (IL)-2 signaling plays a pivotal role in the activation of immune responses, and drugs that block this pathway have been shown to be effective for the immunosuppression in patients with organ transplantation to alleviate/eliminate allograft rejection. The first humanized monoclonal antibody (mAb) daclizumab falls into this category and shows high specificity and affinity against a key component of the IL-2 receptor complex, namely IL-2Ralpha. To reveal the molecular mechanism of the inhibition of the IL-2 signaling pathway by daclizumab, we determined the crystal structures of the daclizumab Fab in free form and in complex with the IL-2Ralpha ectodomain at 2.6 and 2.8 A resolution, respectively. The daclizumab Fab adopts a similar conformation in the presence or absence of the IL-2Ralpha ectodomain. The antigen-binding site of daclizumab is mainly composed of five complementarity determining regions (CDRs) that form a large positively charged surface depression and two flanking patches that are generally hydrophobic. The conformational epitope consists of several discontinuous segments of the IL-2Ralpha ectodomain, a large portion of which overlaps with the regions that interact with IL-2, suggesting that the binding of daclizumab to IL-2Ralpha would prevent the IL-2 binding to IL-2Ralpha and the subsequent formation of the IL-2/IL-2Ralphabetagamma(c) complex, and therefore block the IL-2 signaling pathway. These results also have implications for the design and development of improved mAb drugs targeting IL-2Ralpha.Cell Research advance online publication 7 September 2010; doi:10.1038/cr.2010.130. Structural basis of immunosuppression by the therapeutic antibody daclizumab.,Yang H, Wang J, Du J, Zhong C, Zhang D, Guo H, Guo Y, Ding J Cell Res. 2010 Sep 7. PMID:20820193[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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