5JCW

Crystal Structure of hGSTP1-1 with Glutathione Adduct of Phenethyl Isothiocyanate

Summary for 5JCW

• Entry DOI: 10.2210/pdb5jcw/pdb
• Related: 5JCU
• Descriptor: Glutathione S-transferase P, L-gamma-glutamyl-S-[(2-phenylethyl)carbamothioyl]-L-cysteinylglycine, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (7 entities in total)
• Functional Keywords: gst, peitc, glutathione adduct, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : P09211
• Total number of polymer chains: 2
• Total formula weight: 48679.05

Authors

Kumari, V.,Ji, X. (deposition date: 2016-04-15, release date: 2016-10-12, Last modification date: 2023-09-27)

Primary citation

Kumari, V.,Dyba, M.A.,Holland, R.J.,Liang, Y.H.,Singh, S.V.,Ji, X.
Irreversible Inhibition of Glutathione S-Transferase by Phenethyl Isothiocyanate (PEITC), a Dietary Cancer Chemopreventive Phytochemical.
Plos One, 11:e0163821-e0163821, 2016

PubMed Abstract: 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.

PubMed: 27684484
DOI: 10.1371/journal.pone.0163821

Experimental method

X-RAY DIFFRACTION (1.945 Å)