5az2: Difference between revisions
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==Crystal structure of the Fab fragment of 9E5, a murine monoclonal antibody specific for human epiregulin== | ==Crystal structure of the Fab fragment of 9E5, a murine monoclonal antibody specific for human epiregulin== | ||
<StructureSection load='5az2' size='340' side='right' caption='[[5az2]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='5az2' size='340' side='right'caption='[[5az2]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5az2]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5az2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AZ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AZ2 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.603Å</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=5az2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5az2 OCA], [https://pdbe.org/5az2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5az2 RCSB], [https://www.ebi.ac.uk/pdbsum/5az2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5az2 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Epiregulin (EPR) is a ligand of the epidermal growth factor (EGF) family that upon binding to its epidermal growth factor receptor (EGFR) stimulates proliferative signaling, especially in colon cancer cells. Here, we describe the three-dimensional structure of the EPR antibody (the 9E5(Fab) fragment) in the presence and absence of EPR. Among the six complementarity-determining regions (CDRs), CDR1-3 in the light chain and CDR2 in the heavy chain predominantly recognize EPR. In particular, CDR3 in the heavy chain dramatically moves with cis-trans isomerization of Pro103. A molecular dynamics simulation and mutational analyses revealed that Arg40 in EPR is a key residue for the specific binding of 9E5 IgG. From ITC analysis, the dissociation constant is determined to be 6.5 nM. Surface plasmon resonance analysis revealed that the dissociation rate of 9E5 IgG is extremely slow. The superimposed structure of 9E5(Fab)-EPR on the known complex structure of EGF-EGFR showed that the 9E5(Fab) paratope overlaps with Domains I and III on the EGFR, which reveals that the 9E5(Fab)-EPR complex could not bind to the EGFR. The 9E5 antibody will also be useful in medicine as a neutralizing antibody specific for colon cancer. | |||
Epiregulin Recognition Mechanisms by Anti-Epiregulin Antibody 9E5: Structural, Functional and Molecular Dynamics Simulation Analyses.,Kado Y, Mizohata E, Nagatoishi S, Iijima M, Shinoda K, Miyafusa T, Nakayama T, Yoshizumi T, Sugiyama A, Kawamura T, Lee YH, Matsumura H, Doi H, Fujitani H, Kodama T, Shibasaki Y, Tsumoto K, Inoue T J Biol Chem. 2015 Dec 1. pii: jbc.M115.656009. PMID:26627827<ref>PMID:26627827</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5az2" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
*[[Sandbox 20009|Sandbox 20009]] | |||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Doi | [[Category: Doi H]] | ||
[[Category: Fujitani | [[Category: Fujitani H]] | ||
[[Category: Iijima | [[Category: Iijima M]] | ||
[[Category: Inoue | [[Category: Inoue T]] | ||
[[Category: Kado | [[Category: Kado Y]] | ||
[[Category: Kawamura | [[Category: Kawamura T]] | ||
[[Category: Kodama | [[Category: Kodama T]] | ||
[[Category: Lee | [[Category: Lee YH]] | ||
[[Category: Matsumura | [[Category: Matsumura H]] | ||
[[Category: Miyafusa | [[Category: Miyafusa T]] | ||
[[Category: Mizohata | [[Category: Mizohata E]] | ||
[[Category: Nagatoishi | [[Category: Nagatoishi S]] | ||
[[Category: Nakayama | [[Category: Nakayama T]] | ||
[[Category: Shibasaki | [[Category: Shibasaki Y]] | ||
[[Category: Shinoda | [[Category: Shinoda K]] | ||
[[Category: Sugiyama | [[Category: Sugiyama A]] | ||
[[Category: Tsumoto | [[Category: Tsumoto K]] | ||
[[Category: Yoshizumi | [[Category: Yoshizumi T]] | ||