5ae2

Ether Lipid-Generating Enzyme AGPS in complex with inhibitor 1e

spinqualitylabelsall models 5ae2, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ae2 is a 4 chain structure with sequence from Cavia porcellus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: FAD, FYC, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ADAS_CAVPO Catalyzes the exchange of an acyl for a long-chain alkyl group and the formation of the ether bond in the biosynthesis of ether phospholipids. Publication Abstract from PubMed Dysregulated ether lipid metabolism is an important hallmark of cancer cells. Previous studies have reported that lowering ether lipid levels by genetic ablation of the ether lipid-generating enzyme alkyl-glycerone phosphate synthase (AGPS) lowers key structural and oncogenic ether lipid levels and alters fatty acid, glycerophospholipid, and eicosanoid metabolism to impair cancer pathogenicity, indicating that AGPS may be a potential therapeutic target for cancer. In this study, we have performed a small-molecule screen to identify candidate AGPS inhibitors. We have identified several lead AGPS inhibitors and have structurally characterized their interactions with the enzyme and show that these inhibitors bind to distinct portions of the active site. We further show that the lead AGPS inhibitor 1a selectively lowers ether lipid levels in several types of human cancer cells and impairs their cellular survival and migration. We provide here the first report of in situ-active pharmacological tools for inhibiting AGPS, which may provide chemical scaffolds for future AGPS inhibitor development for cancer therapy. Discovery of Inhibitors for the Ether Lipid-Generating Enzyme AGPS as Anti-Cancer Agents.,Piano V, Benjamin DI, Valente S, Nenci S, Marrocco B, Mai A, Aliverti A, Nomura DK, Mattevi A ACS Chem Biol. 2015 Sep 4. PMID:26322624 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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