6hn3: Difference between revisions
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<StructureSection load='6hn3' size='340' side='right'caption='[[6hn3]], [[Resolution|resolution]] 1.01Å' scene=''> | <StructureSection load='6hn3' size='340' side='right'caption='[[6hn3]], [[Resolution|resolution]] 1.01Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6hn3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HN3 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6hn3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HN3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HN3 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6hkq|6hkq]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6hkq|6hkq]]</div></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GPX4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Phospholipid-hydroperoxide_glutathione_peroxidase Phospholipid-hydroperoxide glutathione peroxidase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=6hn3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hn3 OCA], [https://pdbe.org/6hn3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hn3 RCSB], [https://www.ebi.ac.uk/pdbsum/6hn3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hn3 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). | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Wild-type human glutathione peroxidase 4 (GPX4) was co-expressed with SBP2 (selenocysteine insertion sequence-binding protein 2) in human HEK cells to achieve efficient production of this selenocysteine-containing enzyme on a preparative scale for structural biology. The protein was purified and crystallized, and the crystal structure of the wild-type form of GPX4 was determined at 1.0 A resolution. The overall fold and the active site are conserved compared with previously determined crystal structures of mutated forms of GPX4. A mass-spectrometry-based approach was developed to monitor the reaction of the active-site selenocysteine Sec46 with covalent inhibitors. This, together with the introduction of a surface mutant (Cys66Ser), enabled the crystal structure determination of GPX4 in complex with the covalent inhibitor ML162 [(S)-enantiomer]. The mass-spectrometry-based approach described here opens the path to further co-complex crystal structures of this potential cancer drug target in complex with covalent inhibitors. | |||
Crystal structures of the selenoprotein glutathione peroxidase 4 in its apo form and in complex with the covalently bound inhibitor ML162.,Moosmayer D, Hilpmann A, Hoffmann J, Schnirch L, Zimmermann K, Badock V, Furst L, Eaton JK, Viswanathan VS, Schreiber SL, Gradl S, Hillig RC Acta Crystallogr D Struct Biol. 2021 Feb 1;77(Pt 2):237-248. doi:, 10.1107/S2059798320016125. Epub 2021 Jan 26. PMID:33559612<ref>PMID:33559612</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6hn3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Glutathione peroxidase|Glutathione peroxidase]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Phospholipid-hydroperoxide glutathione peroxidase]] | [[Category: Phospholipid-hydroperoxide glutathione peroxidase]] | ||
Revision as of 09:50, 17 March 2021
wildtype form (apo) of human GPX4 with Se-Cys46wildtype form (apo) of human GPX4 with Se-Cys46
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 PubMedWild-type human glutathione peroxidase 4 (GPX4) was co-expressed with SBP2 (selenocysteine insertion sequence-binding protein 2) in human HEK cells to achieve efficient production of this selenocysteine-containing enzyme on a preparative scale for structural biology. The protein was purified and crystallized, and the crystal structure of the wild-type form of GPX4 was determined at 1.0 A resolution. The overall fold and the active site are conserved compared with previously determined crystal structures of mutated forms of GPX4. A mass-spectrometry-based approach was developed to monitor the reaction of the active-site selenocysteine Sec46 with covalent inhibitors. This, together with the introduction of a surface mutant (Cys66Ser), enabled the crystal structure determination of GPX4 in complex with the covalent inhibitor ML162 [(S)-enantiomer]. The mass-spectrometry-based approach described here opens the path to further co-complex crystal structures of this potential cancer drug target in complex with covalent inhibitors. Crystal structures of the selenoprotein glutathione peroxidase 4 in its apo form and in complex with the covalently bound inhibitor ML162.,Moosmayer D, Hilpmann A, Hoffmann J, Schnirch L, Zimmermann K, Badock V, Furst L, Eaton JK, Viswanathan VS, Schreiber SL, Gradl S, Hillig RC Acta Crystallogr D Struct Biol. 2021 Feb 1;77(Pt 2):237-248. doi:, 10.1107/S2059798320016125. Epub 2021 Jan 26. PMID:33559612[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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