6hkq | pdb_00006hkq

Human GPX4 in complex with covalent Inhibitor ML162 (S enantiomer)

spinqualitylabelsall models 6hkq, resolution 1.54Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6hkq is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.54Å Ligands: DMS, EDO, G9N, SO4 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 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glutathione peroxidase

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