4ps4

From Proteopedia

(Difference between revisions)

Revision as of 11:52, 11 August 2016

Crystal structure of the complex between IL-13 and M1295 FAB

Structural highlights

4ps4 is a 3 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 3l5y. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Related:	3l5w, 3l5x
Gene:	IL13, NC30 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[IL13_HUMAN] Defects in IL13 may be a cause of susceptibility to allergic rhinitis (ALRH) [MIM:607154]. Allergic rhinitis is a common disease of complex inheritance and is characterized by mucosal inflammation caused by allergen exposure.

Function

[IL13_HUMAN] Cytokine. Inhibits inflammatory cytokine production. Synergizes with IL2 in regulating interferon-gamma synthesis. May be critical in regulating inflammatory and immune responses.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. Human framework adaptation of a mouse anti-human IL-13 antibody. J Mol Biol. 2010 Apr 30;398(2):214-31. Epub 2010 Mar 10. PMID:20226193 doi:10.1016/j.jmb.2010.03.004

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ps4"

@@ Line 1: / Line 1: @@
 ==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=''>
@@ Line 6: / Line 7: @@
 <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>
+<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://pdbe.org/4ps4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ps4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ps4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ps4 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4ps4" style="background-color:#fffaf0;"></div>
 ==See Also==

4ps4

From Proteopedia

Revision as of 11:52, 11 August 2016

Crystal structure of the complex between IL-13 and M1295 FAB

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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