Irreversible Inhibition of Glutathione S-Transferase by Phenethyl Isothiocyanate (PEITC), a Dietary Cancer Chemopreventive Phytochemical [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 637.1 Milk processing
• Thông tin xuất bản: Bethesda, Md. : Oak Ridge, Tenn. : National Institutes of Health (U.S.) ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2016
• Mô tả vật lý: Size: Article No. e0163821 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 260796
• Chủ đề: 1. 60 applied life sciences; 2. Cancer prevention; 3. Crystal structure; 4. Cysteine; 5. Dimers (chemical physics); 6. Enzyme inhibitors; 7. Enzymes; 8. Glutathione chromatography; 9. Nitrogen

Tóm tắt

Dietary isothiocyanates abundant as glucosinolate precursors in many edible cruciferous vegetables are effective for prevention of cancer in chemically-induced and transgenic rodent models. Some of these agents, including phenethyl isothiocyanate (PEITC), have already advanced to clinical investigations. The primary route of isothiocyanate metabolism is its conjugation with glutathione (GSH), a reaction catalyzed by glutathione S-transferase (GST). The pi class GST of subunit type 1 (hGSTP1) is much more effective than the alpha class GST of subunit type 1 (hGSTA1) in catalyzing the conjugation. Here, we report the crystal structures of hGSTP1 and hGSTA1 each in complex with the GSH adduct of PEITC. We find that PEITC also covalently modifies the cysteine side chains of GST, which irreversibly inhibits enzymatic activity.