5V3Q

Human GSTO1-1 complexed with ML175

Summary for 5V3Q

• Entry DOI: 10.2210/pdb5v3q/pdb
• Related: 1EEM 3VLN 4IS0
• Descriptor: Glutathione S-transferase omega-1, N-{3-[(2-chloro-acetyl)-(4-nitro-phenyl)-amino]-propyl}-2,2,2-trifluoro-acetamide, SULFATE ION, ... (4 entities in total)
• Functional Keywords: glutathione transferase, inhibitor, ml175, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm, cytosol : P78417
• Total number of polymer chains: 1
• Total formula weight: 28159.68

Authors

Oakley, A.J. (deposition date: 2017-03-07, release date: 2017-12-20, Last modification date: 2024-11-20)

Primary citation

Menon, D.,Innes, A.,Oakley, A.J.,Dahlstrom, J.E.,Jensen, L.M.,Brustle, A.,Tummala, P.,Rooke, M.,Casarotto, M.G.,Baell, J.B.,Nguyen, N.,Xie, Y.,Cuellar, M.,Strasser, J.,Dahlin, J.L.,Walters, M.A.,Burgio, G.,O'Neill, L.A.J.,Board, P.G.
GSTO1-1 plays a pro-inflammatory role in models of inflammation, colitis and obesity.
Sci Rep, 7:17832-17832, 2017

PubMed Abstract: Glutathione 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.

PubMed: 29259211
DOI: 10.1038/s41598-017-17861-6

Experimental method

X-RAY DIFFRACTION (2.25 Å)