5h5s

From Proteopedia

(Difference between revisions)

Revision as of 10:12, 26 February 2020

Crystal structure of human GPX4 in complex with GXpep-3

Structural highlights

5h5s is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	5h5q, 5h5r
Gene:	GPX4 (HUMAN)
Activity:	Phospholipid-hydroperoxide glutathione peroxidase, with EC number 1.11.1.12
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5h5s"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human GPX4 in complex with GXpep-3==
-<StructureSection load='5h5s' size='340' side='right' caption='[[5h5s]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
+<StructureSection load='5h5s' size='340' side='right'caption='[[5h5s]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5h5s]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H5S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5H5S FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5h5s]] 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=5H5S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5H5S 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>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5h5q|5h5q]], [[5h5r|5h5r]]</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=5h5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h5s OCA], [http://pdbe.org/5h5s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5h5s RCSB], [http://www.ebi.ac.uk/pdbsum/5h5s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5h5s ProSAT]</span></td></tr>
@@ Line 25: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Phospholipid-hydroperoxide glutathione peroxidase]]
 [[Category: Kadotani, A]]

5h5s

From Proteopedia

Revision as of 10:12, 26 February 2020

Crystal structure of human GPX4 in complex with GXpep-3

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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