8ghp: Difference between revisions
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The entry | ==GUCY2C-ECD bound to anti-GUCY2C-scFv antibody== | ||
<StructureSection load='8ghp' size='340' side='right'caption='[[8ghp]], [[Resolution|resolution]] 3.52Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8ghp]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GHP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GHP 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]] 3.52Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=8ghp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ghp OCA], [https://pdbe.org/8ghp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ghp RCSB], [https://www.ebi.ac.uk/pdbsum/8ghp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ghp ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/GUC2C_HUMAN GUC2C_HUMAN] Chronic infantile diarrhea due to guanylate cyclase 2C overactivity;Intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency;Congenital sodium diarrhea. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GUC2C_HUMAN GUC2C_HUMAN] Guanylyl cyclase that catalyzes synthesis of cyclic GMP (cGMP) from GTP (PubMed:1718270, PubMed:11950846, PubMed:23269669, PubMed:22521417, PubMed:22436048). Receptor for the E.coli heat-stable enterotoxin; E.coli enterotoxin markedly stimulates the accumulation of cGMP in mammalian cells expressing GUCY2C (PubMed:1718270, PubMed:1680854). Also activated by the endogenous peptides guanylin and uroguanylin (PubMed:8381596).<ref>PMID:11950846</ref> <ref>PMID:1680854</ref> <ref>PMID:1718270</ref> <ref>PMID:22436048</ref> <ref>PMID:22521417</ref> <ref>PMID:23269669</ref> <ref>PMID:8381596</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The intestinal epithelial receptor Guanylyl Cyclase C (GUCY2C) is a tumor-associated cell surface antigen expressed across gastrointestinal malignancies that can serve as an efficacious target for colorectal cancer immunotherapy. Here, we describe a yeast surface-display approach combined with an orthogonal peptide-based mapping strategy to identify the GUCY2C binding epitope of a novel anti-GUCY2CxCD3 bispecific antibody (BsAb) that recently advanced into the clinic for the treatment of cancer. The target epitope was localized to the N-terminal helix H2 of human GUCY2C, which enabled the determination of the crystal structure of the minimal GUCY2C epitope in complex with the anti-GUCY2C antibody domain. To understand if this minimal epitope covers the entire antibody binding region and to investigate the impact of epitope position on the antibody's activity, we further determined the structure of this interaction in the context of the full-length extracellular domain (ECD) of GUCY2C. We found that this epitope is positioned on the protruding membrane-distal helical region of GUCY2C and that its specific location on the surface of GUCY2C dictates the close spatial proximity of the two antigen arms in a diabody arrangement essential to the tumor killing activity of GUCY2CxCD3 BsAb. | |||
Molecular insights into recognition of GUCY2C by T-cell engaging bispecific antibody anti-GUCY2CxCD3.,Rampuria P, Mosyak L, Root AR, Svenson K, Agostino MJ, LaVallie ER Sci Rep. 2023 Aug 17;13(1):13408. doi: 10.1038/s41598-023-40467-0. PMID:37591971<ref>PMID:37591971</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8ghp" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mosyak L]] | |||