8jyr: Difference between revisions

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'''Unreleased structure'''


The entry 8jyr is ON HOLD  until 2025-07-03
==Crystal structure of anti-HER2 antibody H2Mab-119 in complex with HER2 domain I==
<StructureSection load='8jyr' size='340' side='right'caption='[[8jyr]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8jyr]] is a 3 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=8JYR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JYR 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]] 1.69&#8491;</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=8jyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jyr OCA], [https://pdbe.org/8jyr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jyr RCSB], [https://www.ebi.ac.uk/pdbsum/8jyr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jyr ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Overexpression of human epidermal growth factor receptor 2 (HER2) in breast and gastric cancers is associated with a poor prognosis, making it an important therapeutic target. Here, we establish a novel cancer-specific anti-HER2 antibody, H(2)Mab-214. H(2)Mab-214 reacts with HER2 on cancer cells, but unlike the therapeutic antibody trastuzumab, it does not react with HER2 on normal cells in flow cytometry measurements. A crystal structure suggests that H(2)Mab-214 recognizes a structurally disrupted region in the HER2 domain IV, which normally forms a beta-sheet. We show that this misfolding is inducible by site-directed mutagenesis mimicking the disulfide bond defects that also may occur in cancer cells, indicating that the local misfolding in the Cys-rich domain IV governs the cancer-specificity of H(2)Mab-214. Furthermore, we show that H(2)Mab-214 effectively suppresses tumor growth in xenograft mouse models. Our findings offer a potential strategy for developing cancer-specific therapeutic antibodies that target partially misfolded cell surface receptors.


Authors:  
Locally misfolded HER2 expressed on cancer cells is a promising target for development of cancer-specific antibodies.,Arimori T, Mihara E, Suzuki H, Ohishi T, Tanaka T, Kaneko MK, Takagi J, Kato Y Structure. 2024 May 2;32(5):536-549.e5. doi: 10.1016/j.str.2024.02.007. Epub 2024 , Mar 8. PMID:38460519<ref>PMID:38460519</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 8jyr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Arimori T]]
[[Category: Takagi J]]
Retrieved from "https://proteopedia.org/8jyr"