5v3q
From Proteopedia
Human GSTO1-1 complexed with ML175
Structural highlights
FunctionGSTO1_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.[1] [2] [3] [4] [5] Publication Abstract from PubMedGlutathione transferase Omega 1 (GSTO1-1) is an atypical GST reported to play a pro-inflammatory role in response to LPS. Here we show that genetic knockout of Gsto1 alters the response of mice to three distinct inflammatory disease models. GSTO1-1 deficiency ameliorates the inflammatory response stimulated by LPS and attenuates the inflammatory impact of a high fat diet on glucose tolerance and insulin resistance. In contrast, GSTO1-1 deficient mice show a more severe inflammatory response and increased escape of bacteria from the colon into the lymphatic system in a dextran sodium sulfate mediated model of inflammatory bowel disease. These responses are similar to those of TLR4 and MyD88 deficient mice in these models and confirm that GSTO1-1 is critical for a TLR4-like pro-inflammatory response in vivo. In wild-type mice, we show that a small molecule inhibitor that covalently binds in the active site of GSTO1-1 can be used to ameliorate the inflammatory response to LPS. Our findings demonstrate the potential therapeutic utility of GSTO1-1 inhibitors in the modulation of inflammation and suggest their possible application in the treatment of a range of inflammatory conditions. GSTO1-1 plays a pro-inflammatory role in models of inflammation, colitis and obesity.,Menon D, Innes A, Oakley AJ, Dahlstrom JE, Jensen LM, Brustle A, Tummala P, Rooke M, Casarotto MG, Baell JB, Nguyen N, Xie Y, Cuellar M, Strasser J, Dahlin JL, Walters MA, Burgio G, O'Neill LAJ, Board PG Sci Rep. 2017 Dec 19;7(1):17832. doi: 10.1038/s41598-017-17861-6. PMID:29259211[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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