7y99

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<table><tr><td colspan='2'>[[7y99]] is a 2 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=7Y99 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y99 FirstGlance]. <br>
<table><tr><td colspan='2'>[[7y99]] is a 2 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=7Y99 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y99 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]] 1.9&#8491;</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]] 1.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IQ8:N-(2-acetamidoethyl)-4-(4,5-dihydro-1,3-thiazol-2-yl)benzamide'>IQ8</scene></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IQ8:~{N}-(2-acetamidoethyl)-4-(4,5-dihydro-1,3-thiazol-2-yl)benzamide'>IQ8</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=7y99 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y99 OCA], [https://pdbe.org/7y99 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y99 RCSB], [https://www.ebi.ac.uk/pdbsum/7y99 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y99 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=7y99 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y99 OCA], [https://pdbe.org/7y99 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y99 RCSB], [https://www.ebi.ac.uk/pdbsum/7y99 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y99 ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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<div style="background-color:#fffaf0;">
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[https://www.uniprot.org/uniprot/B2CL1_MOUSE B2CL1_MOUSE] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.<ref>PMID:9390687</ref> Isoform Bcl-X(S) promotes apoptosis (By similarity).<ref>PMID:9390687</ref>
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== Publication Abstract from PubMed ==
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Overexpressed pro-survival B-cell lymphoma-2 (BCL-2) family proteins BCL-2 and BCL-X(L) can render tumor cells malignant. Leukemia drug venetoclax is currently the only approved selective BCL-2 inhibitor. However, its application has led to an emergence of resistant mutations, calling for drugs with an innovative mechanism of action. Herein we present cyclic peptides (CPs) with nanomolar-level binding affinities to BCL-2 or BCL-X(L), and further reveal the structural and functional mechanisms of how these CPs target two proteins in a fashion that is remarkably different from traditional small-molecule inhibitors. In addition, these CPs can bind to the venetoclax-resistant clinical BCL-2 mutants with similar affinities as to the wild-type protein. Furthermore, we identify a single-residue discrepancy between BCL-2 D111 and BCL-X(L) A104 as a molecular "switch" that can differently engage CPs. Our study suggests that CPs may inhibit BCL-2 or BCL-X(L) by delicately modulating protein-protein interactions, potentially benefiting the development of next-generation therapeutics.
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Cyclic peptides discriminate BCL-2 and its clinical mutants from BCL-X(L) by engaging a single-residue discrepancy.,Li F, Liu J, Liu C, Liu Z, Peng X, Huang Y, Chen X, Sun X, Wang S, Chen W, Xiong D, Diao X, Wang S, Zhuang J, Wu C, Wu D Nat Commun. 2024 Feb 17;15(1):1476. doi: 10.1038/s41467-024-45848-1. PMID:38368459<ref>PMID:38368459</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7y99" style="background-color:#fffaf0;"></div>
== References ==
== References ==
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Current revision

Crystal Structure Analysis of cp2 bound BCLxl

PDB ID 7y99

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