5H5R: Crystal Structure Of Human Gpx4 In Complex With Gxpep-2

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.
PDB ID: 5H5RDownload
MMDB ID: 145420
PDB Deposition Date: 2016/11/9
Updated in MMDB: 2016/12
Experimental Method:
x-ray diffraction
Resolution: 1.2  Å
Source Organism:
Enterobacteria phage T7
Similar Structures:
Biological Unit for 5H5R: dimeric; determined by author
Molecular Components in 5H5R
Label Count Molecule
Proteins (2 molecules)
Phospholipid Hydroperoxide Glutathione Peroxidase, Mitochondrial(Gene symbol: GPX4)
Molecule annotation
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB