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• W3136377147 abstract "Abstract Microsomal glutathione S-transferase 2 (MGST2) produces leukotriene C 4 , key for intracrine signaling of endoplasmic reticulum (ER) stress, oxidative DNA damage and cell death. MGST2 trimer restricts catalysis to only one out of three active sites at a time, but the molecular basis is unknown. Here, we present crystal structures of human MGST2 combined with biochemical and computational evidence for a concerted mechanism, involving local unfolding coupled to global conformational changes that regulate catalysis. Furthermore, synchronized changes in the biconical central pore modulate the hydrophobicity and control solvent influx to optimize reaction conditions at the active site. These unique mechanistic insights pertain to other, structurally related, drug targets." @default.
• W3136377147 created "2021-03-29" @default.
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• W3136377147 date "2021-03-19" @default.
• W3136377147 modified "2023-10-15" @default.
• W3136377147 title "Crystal structures of human MGST2 reveal synchronized conformational changes regulating catalysis" @default.
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• W3136377147 doi "https://doi.org/10.1038/s41467-021-21924-8" @default.
• W3136377147 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7979937" @default.
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