8C5D

Glutathione transferase P1-1 from Mus musculus

8C5D の概要

• エントリーDOI: 10.2210/pdb8c5d/pdb
• 分子名称: Glutathione S-transferase P 1, GLYCEROL, S-(P-NITROBENZYL)GLUTATHIONE, ... (7 entities in total)
• 機能のキーワード: multidrug resistance, pesticide, enzyme inhibition, drug design, transferase
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48788.05

構造登録者

Papageorgiou, A.C. (登録日: 2023-01-06, 公開日: 2023-05-24, 最終更新日: 2024-06-19)

主引用文献

Kupreienko, O.,Pouliou, F.,Konstandinidis, K.,Axarli, I.,Douni, E.,Papageorgiou, A.C.,Labrou, N.E.
Inhibition Analysis and High-Resolution Crystal Structure of Mus musculus Glutathione Transferase P1-1.
Biomolecules, 13:-, 2023

PubMed Abstract: Multidrug resistance is a significant barrier that makes anticancer therapies less effective. Glutathione transferases (GSTs) are involved in multidrug resistance mechanisms and play a significant part in the metabolism of alkylating anticancer drugs. The purpose of this study was to screen and select a lead compound with high inhibitory potency against the isoenzyme GSTP1-1 from (GSTP1-1). The lead compound was selected following the screening of a library of currently approved and registered pesticides that belong to different chemical classes. The results showed that the fungicide iprodione [3-(3,5-dichlorophenyl)-2,4-dioxo-N-propan-2-ylimidazolidine-1-carboxamide] exhibited the highest inhibition potency (ΙC = 11.3 ± 0.5 μΜ) towards GSTP1-1. Kinetics analysis revealed that iprodione functions as a mixed-type inhibitor towards glutathione (GSH) and non-competitive inhibitor towards 1-chloro-2,4-dinitrobenzene (CDNB). X-ray crystallography was used to determine the crystal structure of GSTP1-1 at 1.28 Å resolution as a complex with S-(p-nitrobenzyl)glutathione (Nb-GSH). The crystal structure was used to map the ligand-binding site of GSTP1-1 and to provide structural data of the interaction of the enzyme with iprodione using molecular docking. The results of this study shed light on the inhibition mechanism of GSTP1-1 and provide a new compound as a potential lead structure for future drug/inhibitor development.

PubMed: 37189361
DOI: 10.3390/biom13040613

実験手法

X-RAY DIFFRACTION (1.28 Å)