4yqv

Glutathione S-transferase Omega 1 bound to covalent inhibitor C4-10

spinqualitylabelsall models 4yqv, resolution 2.06Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4yqv is a 3 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 2.06Å Ligands: 4GG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GSTO1_HUMAN Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities. Has S-(phenacyl)glutathione reductase activity. Has also glutathione S-transferase activity. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA) and dimethylarsonic acid. Publication Abstract from PubMed Glutathione S-transferase omega 1 (GSTO1) is an atypical GST isoform that is overexpressed in several cancers and has been implicated in drug resistance. Currently, no small-molecule drug targeting GSTO1 is under clinical development. Here we show that silencing of GSTO1 with siRNA significantly impairs cancer cell viability, validating GSTO1 as a potential new target in oncology. We report on the development and characterization of a series of chloroacetamide-containing potent GSTO1 inhibitors. Co-crystal structures of GSTO1 with our inhibitors demonstrate covalent binding to the active site cysteine. These potent GSTO1 inhibitors suppress cancer cell growth, enhance the cytotoxic effects of cisplatin and inhibit tumour growth in colon cancer models as single agent. Bru-seq-based transcription profiling unravelled novel roles for GSTO1 in cholesterol metabolism, oxidative and endoplasmic stress responses, cytoskeleton and cell migration. Our findings demonstrate the therapeutic utility of GSTO1 inhibitors as anticancer agents and identify the novel cellular pathways under GSTO1 regulation in colorectal cancer. Mechanistic evaluation and transcriptional signature of a glutathione S-transferase omega 1 inhibitor.,Ramkumar K, Samanta S, Kyani A, Yang S, Tamura S, Ziemke E, Stuckey JA, Li S, Chinnaswamy K, Otake H, Debnath B, Yarovenko V, Sebolt-Leopold JS, Ljungman M, Neamati N Nat Commun. 2016 Oct 5;7:13084. doi: 10.1038/ncomms13084. PMID:27703239 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glutathione S-transferase 3D structures

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