7kkh: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7kkh]] is a 2 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=7KKH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KKH FirstGlance]. <br> | <table><tr><td colspan='2'>[[7kkh]] is a 2 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=7KKH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KKH FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=91S:(S)-1-{4-[6-chloro-8-fluoro-7-(2-fluoro-6-hydroxyphenyl)quinazolin-4-yl]+piperazin-1-yl}propan-1-one'>91S</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=91S:(S)-1-{4-[6-chloro-8-fluoro-7-(2-fluoro-6-hydroxyphenyl)quinazolin-4-yl]+piperazin-1-yl}propan-1-one'>91S</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=7kkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kkh OCA], [https://pdbe.org/7kkh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kkh RCSB], [https://www.ebi.ac.uk/pdbsum/7kkh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kkh ProSAT]</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=7kkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kkh OCA], [https://pdbe.org/7kkh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kkh RCSB], [https://www.ebi.ac.uk/pdbsum/7kkh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kkh ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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</div> | </div> | ||
<div class="pdbe-citations 7kkh" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7kkh" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Latest revision as of 18:26, 18 October 2023
P1A4 Fab in complex with ARS1620P1A4 Fab in complex with ARS1620
Structural highlights
Publication Abstract from PubMedImmunotargeting of tumor-specific antigens is a powerful therapeutic strategy. Immunotherapies directed at MHC-I complexes have expanded the scope of antigens and enabled the direct targeting of intracellular oncoproteins at the cell surface. We asked whether covalent drugs that alkylate mutated residues on oncoproteins could act as haptens to generate unique MHC-I-restricted neoantigens. Here, we report that KRAS G12C mutant cells treated with the covalent inhibitor ARS1620 present ARS1620-modified peptides in MHC-I complexes. Using ARS1620-specific antibodies identified by phage display, we show that these haptenated MHC-I complexes can serve as tumor-specific neoantigens and that a bispecific T cell engager construct based on a hapten-specific antibody elicits a cytotoxic T cell response against KRAS G12C cells, including those resistant to direct KRAS G12C inhibition. With multiple K-RAS G12C inhibitors in clinical use or undergoing clinical trials, our results present a strategy to enhance their efficacy and overcome the rapidly arising tumor resistance. A covalent inhibitor of K-Ras(G12C) induces MHC class I presentation of haptenated peptide neoepitopes targetable by immunotherapy.,Zhang Z, Rohweder PJ, Ongpipattanakul C, Basu K, Bohn MF, Dugan EJ, Steri V, Hann B, Shokat KM, Craik CS Cancer Cell. 2022 Sep 12;40(9):1060-1069.e7. doi: 10.1016/j.ccell.2022.07.005. PMID:36099883[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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