View source for 6elw


==High resolution structure of selenocysteine containing human GPX4==
<StructureSection load='6elw' size='340' side='right' caption='[[6elw]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6elw]] is a 1 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=6ELW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ELW 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></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SE7:2-AMINO-3-SELENINO-PROPIONIC+ACID'>SE7</scene></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=6elw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6elw OCA], [http://pdbe.org/6elw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6elw RCSB], [http://www.ebi.ac.uk/pdbsum/6elw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6elw ProSAT]</span></td></tr>
</table>
== 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). 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Glutathione peroxidases (GPX) are anti-oxidative enzymes that reduce organic and inorganic hydroperoxides to the corresponding alcohols at the expense of reduced glutathione. The human genome involves eight GPX genes and five of them encode for selenocysteine-containing enzymes. Among the human GPX-isoforms, GPX4 is unique since it is capable of reducing complex hydroperoxy ester lipids such as hydroperoxy phospholipids and hydroperoxy cholesterolesters. Using a number of genetically modified mouse strains the biological role of GPX4 has comprehensively characterized but the molecular enzymology is less well explored. This lack of knowledge is partly related to the fact that mammalian selenoproteins are not high-level expressed in conventional overexpression systems. To explore the structural and functional properties of human GPX4 we expressed this selenoprotein in a cysteine-auxotrophic E. coli strain using a semi-chemical expression strategy. The recombinant enzyme was purified in mg amounts from the bacterial lysate to electrophoretic homogeneity and characterized with respect to its protein-chemical and enzymatic properties. Its crystal structure was solved at 1.3A resolution and the X-ray data indicated a monomeric protein, which contains the catalytic selenium at the redox level of the seleninic acid. These data suggest an alternative reaction mechanism involving three different redox states (selenol, selenenic acid, seleninic acid) of the catalytically active selenocysteine.

Crystal structure and functional characterization of selenocysteine-containing glutathione peroxidase 4 suggests an alternative mechanism of peroxide reduction.,Borchert A, Kalms J, Roth SR, Rademacher M, Schmidt A, Holzhutter HG, Kuhn H, Scheerer P Biochim Biophys Acta. 2018 Jun 5. pii: S1388-1981(18)30127-6. doi:, 10.1016/j.bbalip.2018.06.006. PMID:29883798<ref>PMID:29883798</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6elw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Phospholipid-hydroperoxide glutathione peroxidase]]
[[Category: Borchert, A]]
[[Category: Kalms, J]]
[[Category: Kuhn, H]]
[[Category: Scheerer, P]]
[[Category: Anti-oxidatve defense system]]
[[Category: Human gpx4]]
[[Category: Oxidoreductase]]
[[Category: Peroxidase]]
[[Category: Selenoprotein]]
[[Category: Thioredoxin-fold]]