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| | <StructureSection load='5h5r' size='340' side='right'caption='[[5h5r]], [[Resolution|resolution]] 1.20Å' scene=''> | | <StructureSection load='5h5r' size='340' side='right'caption='[[5h5r]], [[Resolution|resolution]] 1.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5h5r]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H5R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5H5R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5h5r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_phage_T7 Escherichia phage T7] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H5R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5H5R FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5h5q|5h5q]], [[5h5s|5h5s]]</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=5h5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h5r OCA], [https://pdbe.org/5h5r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5h5r RCSB], [https://www.ebi.ac.uk/pdbsum/5h5r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5h5r ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GPX4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phospholipid-hydroperoxide_glutathione_peroxidase Phospholipid-hydroperoxide glutathione peroxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.12 1.11.1.12] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5h5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h5r OCA], [http://pdbe.org/5h5r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5h5r RCSB], [http://www.ebi.ac.uk/pdbsum/5h5r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5h5r ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5h5r" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5h5r" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Glutathione peroxidase|Glutathione peroxidase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Escherichia phage T7]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Phospholipid-hydroperoxide glutathione peroxidase]]
| + | [[Category: Kadotani A]] |
| - | [[Category: Kadotani, A]] | + | [[Category: Lane W]] |
| - | [[Category: Lane, W]] | + | [[Category: Snell G]] |
| - | [[Category: Snell, G]] | + | [[Category: Sogabe S]] |
| - | [[Category: Sogabe, S]] | + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
| + | |
| - | [[Category: Phospholipid hydroperoxide glutathione peroxidase 4]]
| + | |
| - | [[Category: Selenocysteine]]
| + | |
| Structural highlights
Function
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).
Publication Abstract from PubMed
The phospholipid hydroperoxidase glutathione peroxidase (GPX4) is an enzyme that reduces lipid hydroperoxides in lipid membranes. Recently, GPX4 has been investigated as a target molecule that induces iron-dependent cell death (ferroptosis) selectively in cancer cells that express mutant Ras. GPX4 inhibitors have the potential to become novel anti-cancer drugs. However, there are no druggable pockets for conventional small molecules on the molecular surface of GPX4. To generate GPX4 inhibitors, we examined the use of peptides as an alternative to small molecules. By screening peptide libraries displayed on T7 phages, and analyzing the X-ray crystal structures of the peptides, we successfully identified one peptide that binds to near Sec73 of catalytic site and two peptides that bind to another site on GPX4. To our knowledge, this is the first study reporting GPX4 inhibitory peptides and their structural information.
Discovery of GPX4 inhibitory peptides from random peptide T7 phage display and subsequent structural analysis.,Sakamoto K, Sogabe S, Kamada Y, Matsumoto SI, Kadotani A, Sakamoto JI, Tani A Biochem Biophys Res Commun. 2016 Nov 9. pii: S0006-291X(16)31890-3. doi:, 10.1016/j.bbrc.2016.11.035. PMID:27836545[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sakamoto K, Sogabe S, Kamada Y, Matsumoto SI, Kadotani A, Sakamoto JI, Tani A. Discovery of GPX4 inhibitory peptides from random peptide T7 phage display and subsequent structural analysis. Biochem Biophys Res Commun. 2016 Nov 9. pii: S0006-291X(16)31890-3. doi:, 10.1016/j.bbrc.2016.11.035. PMID:27836545 doi:http://dx.doi.org/10.1016/j.bbrc.2016.11.035
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