7u4n
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7u4n]] 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=7U4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U4N FirstGlance]. <br> | <table><tr><td colspan='2'>[[7u4n]] 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=7U4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U4N FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L8X:methyl+( | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L8X:methyl+(1~{S},3~{R})-2-(2-chloranylethanoyl)-1-(4-methoxycarbonylphenyl)-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylate'>L8X</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=7u4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u4n OCA], [https://pdbe.org/7u4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u4n RCSB], [https://www.ebi.ac.uk/pdbsum/7u4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u4n 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=7u4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u4n OCA], [https://pdbe.org/7u4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u4n RCSB], [https://www.ebi.ac.uk/pdbsum/7u4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u4n ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/GPX4_HUMAN GPX4_HUMAN] Protects cells against membrane lipid peroxidation and cell death. Required for normal sperm development and male fertility. Could play a major role in protecting mammals from the toxicity of ingested lipid hydroperoxides. Essential for embryonic development. Protects from radiation and oxidative damage (By similarity). | [https://www.uniprot.org/uniprot/GPX4_HUMAN GPX4_HUMAN] Protects cells against membrane lipid peroxidation and cell death. Required for normal sperm development and male fertility. Could play a major role in protecting mammals from the toxicity of ingested lipid hydroperoxides. Essential for embryonic development. Protects from radiation and oxidative damage (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Encouraged by the dependence of drug-resistant, metastatic cancers on GPX4, we examined biophysical mechanisms of GPX4 inhibition, which revealed an unexpected allosteric site. We found that this site was involved in native regeneration of GPX4 under low glutathione conditions. Covalent binding of inhibitors to this allosteric site caused a conformational change, inhibition of activity, and subsequent cellular GPX4 protein degradation. To verify this site in an unbiased manner, we screened a library of compounds and identified and validated that an additional compound can covalently bind in this allosteric site, inhibiting and degrading GPX4. We determined co-crystal structures of six different inhibitors bound in this site. We have thus identified an allosteric mechanism for small molecules targeting aggressive cancers dependent on GPX4. | ||
| + | |||
| + | Small-molecule allosteric inhibitors of GPX4.,Liu H, Forouhar F, Lin AJ, Wang Q, Polychronidou V, Soni RK, Xia X, Stockwell BR Cell Chem Biol. 2022 Dec 15;29(12):1680-1693.e9. doi: , 10.1016/j.chembiol.2022.11.003. Epub 2022 Nov 23. PMID:36423641<ref>PMID:36423641</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7u4n" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of human GPX4-U46C in complex with RSL3
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Categories: Homo sapiens | Large Structures | Forouhar F | Lin AJ | Liu H | Soni RK | Stockwell BR | Wang Q | Xia X
