This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


3l7e

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:32, 6 September 2023) (edit) (undo)
 
(4 intermediate revisions not shown.)
Line 1: Line 1:
 +
==Crystal structure of ANTI-IL-13 antibody C836==
==Crystal structure of ANTI-IL-13 antibody C836==
-
<StructureSection load='3l7e' size='340' side='right' caption='[[3l7e]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+
<StructureSection load='3l7e' size='340' side='right'caption='[[3l7e]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[3l7e]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L7E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L7E FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[3l7e]] is a 4 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=3L7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L7E FirstGlance]. <br>
-
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><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]] 2.5&#8491;</td></tr>
-
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3l5w|3l5w]], [[3l5x|3l5x]], [[3l5y|3l5y]], [[3l7f|3l7f]]</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3l7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l7e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3l7e RCSB], [http://www.ebi.ac.uk/pdbsum/3l7e PDBsum]</span></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=3l7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l7e OCA], [https://pdbe.org/3l7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l7e RCSB], [https://www.ebi.ac.uk/pdbsum/3l7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l7e ProSAT]</span></td></tr>
-
<table>
+
</table>
-
<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.
+
-
 
+
-
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>
+
-
 
+
-
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
== References ==
+
-
<references/>
+
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Lk3 transgenic mice]]
+
[[Category: Homo sapiens]]
-
[[Category: Gilliland, G L.]]
+
[[Category: Large Structures]]
-
[[Category: Malia, T.]]
+
[[Category: Mus musculus]]
-
[[Category: Obmolova, G.]]
+
[[Category: Gilliland GL]]
-
[[Category: Teplyakov, A.]]
+
[[Category: Malia T]]
-
[[Category: Immune system]]
+
[[Category: Obmolova G]]
-
[[Category: Immunoglobulin fold]]
+
[[Category: Teplyakov A]]
-
[[Category: Monoclonal antibody]]
+

Current revision

Crystal structure of ANTI-IL-13 antibody C836

PDB ID 3l7e

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3l7e"
Personal tools