3iu3: Difference between revisions

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-{{STRUCTURE_3iu3|  PDB=3iu3  |  SCENE=  }}
-===Crystal structure of the Fab fragment of therapeutic antibody Basiliximab in complex with IL-2Ra (CD25) ectodomain===
-{{ABSTRACT_PUBMED_20032294}}
-==Disease==
+==Crystal structure of the Fab fragment of therapeutic antibody Basiliximab in complex with IL-2Ra (CD25) ectodomain==
-[[http://www.uniprot.org/uniprot/IL2RA_HUMAN IL2RA_HUMAN]] Genetic variations in IL2RA are associated with susceptibility to diabetes mellitus insulin-dependent type 10 (IDDM10) [MIM:[http://omim.org/entry/601942 601942]]. A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:17676041</ref>
+<StructureSection load='3iu3' size='340' side='right'caption='[[3iu3]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3iu3]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IU3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IU3 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=3iu3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3iu3 OCA], [https://pdbe.org/3iu3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3iu3 RCSB], [https://www.ebi.ac.uk/pdbsum/3iu3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3iu3 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/IGKC_HUMAN IGKC_HUMAN] Defects in IGKC are the cause of immunoglobulin kappa light chain deficiency (IGKCD) [MIM:[https://omim.org/entry/614102 614102]. IGKCD is a disease characterized by the complete absence of immunoglobulin kappa chains.<ref>PMID:3931219</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/IGKC_HUMAN IGKC_HUMAN]
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/iu/3iu3_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </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/main_output.php?pdb_ID=3iu3 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+IL-2 signaling plays a central role in the initiation and activation of immune responses. Correspondingly, blockage of this pathway leads to inhibition of the immune system and would provide some therapeutic benefits. Basiliximab (Simulect), a therapeutic mAb drug with specificity against IL-2R alpha of T cells, was approved by U.S. Food and Drug Administration in 1998. It has been proven to be effective in the suppression of the IL-2 pathway and hence has been widely used to prevent allograft rejection in organ transplantation, especially in kidney transplants. In this study, we report the crystal structure of the basiliximab Fab in complex with the ectodomain of IL-2R alpha at 2.9 A resolution. In the complex structure, the Fab interacts with IL-2R alpha with extensive hydrophobic and hydrophilic interactions, accounting for a high binding affinity of 0.14 nM. The Ag binding site of basiliximab consists of all six CDR loops that form a large binding interface with a central shallow hydrophobic groove surrounded by four hydrophilic patches. The discontinuous epitope is composed of several segments from the D1 domain and a minor segment from the D2 domain that overlap with most of the regions responsible for the interactions with IL-2. Thus, basiliximab binding can completely block the interactions of IL-2 with IL-2R alpha and hence inhibit the activation of the IL-2 signal pathway. The structural results also provide important implications for the development of improved and new IL-2R alpha-targeted mAb drugs.
-==Function==
+Structural basis for the blockage of IL-2 signaling by therapeutic antibody basiliximab.,Du J, Yang H, Zhang D, Wang J, Guo H, Peng B, Guo Y, Ding J J Immunol. 2010 Feb 1;184(3):1361-8. Epub 2009 Dec 23. PMID:20032294<ref>PMID:20032294</ref>
-[[http://www.uniprot.org/uniprot/IL2RA_HUMAN IL2RA_HUMAN]] Receptor for interleukin-2.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[3iu3]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IU3 OCA].
+</div>
+<div class="pdbe-citations 3iu3" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Interleukin receptor|Interleukin receptor]]
+*[[Interleukin receptor 3D structures|Interleukin receptor 3D structures]]
-*[[Monoclonal Antibody|Monoclonal Antibody]]
+*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:020032294</ref><references group="xtra"/><references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Ding, J.]]
+[[Category: Large Structures]]
-[[Category: Du, J.]]
+[[Category: Mus musculus]]
-[[Category: Wang, J.]]
+[[Category: Ding J]]
-[[Category: Yang, H.]]
+[[Category: Du J]]
-[[Category: Basiliximab]]
+[[Category: Wang J]]
-[[Category: Cd25]]
+[[Category: Yang H]]
-[[Category: Disulfide bond]]
-[[Category: Glycoprotein]]
-[[Category: Il-2ra]]
-[[Category: Immune system]]
-[[Category: Membrane]]
-[[Category: Receptor]]
-[[Category: Simulect]]
-[[Category: Sushi]]
-[[Category: Therapeutic antibody]]
-[[Category: Transmembrane]]