4ps4: Difference between revisions

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-{{STRUCTURE_4ps4|  PDB=4ps4  |  SCENE=  }}
+==Crystal structure of the complex between IL-13 and M1295 FAB==
-===Crystal structure of the complex between IL-13 and M1295 FAB===
+<StructureSection load='4ps4' size='340' side='right' caption='[[4ps4]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
-{{ABSTRACT_PUBMED_20226193}}
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4ps4]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3l5y 3l5y]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PS4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PS4 FirstGlance]. <br>
-==Disease==
+</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3l5w|3l5w]], [[3l5x|3l5x]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL13, NC30 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4ps4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ps4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ps4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ps4 PDBsum]</span></td></tr>
+</table>
+== Disease ==
 [[http://www.uniprot.org/uniprot/IL13_HUMAN IL13_HUMAN]] Defects in IL13 may be a cause of susceptibility to allergic rhinitis (ALRH) [MIM:[http://omim.org/entry/607154 607154]]. Allergic rhinitis is a common disease of complex inheritance and is characterized by mucosal inflammation caused by allergen exposure.
+== Function ==
+[[http://www.uniprot.org/uniprot/IL13_HUMAN IL13_HUMAN]] Cytokine. Inhibits inflammatory cytokine production. Synergizes with IL2 in regulating interferon-gamma synthesis. May be critical in regulating inflammatory and immune responses.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Humanization of a potent neutralizing mouse anti-human IL-13 antibody (m836) using a method called human framework adaptation (HFA) is reported. HFA consists of two steps: human framework selection (HFS) and specificity-determining residue optimization (SDRO). The HFS step involved generation of a library of m836 antigen binding sites combined with diverse human germline framework regions (FRs), which were selected based on structural and sequence similarities between mouse variable domains and a repertoire of human antibody germline genes. SDRO consisted of diversifying specificity-determining residues and selecting variants with improved affinity using phage display. HFS of m836 resulted in a 5-fold loss of affinity, whereas SDRO increased the affinity up to 100-fold compared to the HFS antibody. Crystal structures of Fabs in complex with IL-13 were obtained for m836, the HFS variant chosen for SDRO, and one of the highest-affinity SDRO variants. Analysis of the structures revealed that major conformational changes in FR-H1 and FR-H3 occurred after FR replacement, but none of them had an evident direct impact on residues in contact with IL-13. Instead, subtle changes affected the V(L)/V(H) (variable-light domain/variable-heavy domain) interface and were likely responsible for the 5-fold decreased affinity. After SDRO, increased affinity resulted mainly from rearrangements in hydrogen-bonding pattern at the antibody/antigen interface. Comparison with m836 putative germline genes suggested interesting analogies between natural affinity maturation and the engineering process that led to the potent HFA anti-human IL-13 antibody.
-==Function==
+Human framework adaptation of a mouse anti-human IL-13 antibody.,Fransson J, Teplyakov A, Raghunathan G, Chi E, Cordier W, Dinh T, Feng Y, Giles-Komar J, Gilliland G, Lollo B, Malia TJ, Nishioka W, Obmolova G, Zhao S, Zhao Y, Swanson RV, Almagro JC J Mol Biol. 2010 Apr 30;398(2):214-31. Epub 2010 Mar 10. PMID:20226193<ref>PMID:20226193</ref>
-[[http://www.uniprot.org/uniprot/IL13_HUMAN IL13_HUMAN]] Cytokine. Inhibits inflammatory cytokine production. Synergizes with IL2 in regulating interferon-gamma synthesis. May be critical in regulating inflammatory and immune responses.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[4ps4]] is a 3 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3l5y 3l5y]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PS4 OCA].
+</div>
-==Reference==
+==See Also==
-<ref group="xtra">PMID:020226193</ref><references group="xtra"/><references/>
+*[[Interleukin|Interleukin]]
-[[Category: Gilliland, G L.]]
+== References ==
-[[Category: Malia, T.]]
+<references/>
-[[Category: Obmolova, G.]]
+__TOC__
-[[Category: Teplyakov, A.]]
+</StructureSection>
+[[Category: Human]]
+[[Category: Gilliland, G L]]
+[[Category: Malia, T]]
+[[Category: Obmolova, G]]
+[[Category: Teplyakov, A]]
 [[Category: Alpha-helical bundle]]
 [[Category: Cytokine]]