8C5D
Glutathione transferase P1-1 from Mus musculus
Summary for 8C5D
| Entry DOI | 10.2210/pdb8c5d/pdb |
| Descriptor | Glutathione S-transferase P 1, GLYCEROL, S-(P-NITROBENZYL)GLUTATHIONE, ... (7 entities in total) |
| Functional Keywords | multidrug resistance, pesticide, enzyme inhibition, drug design, transferase |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 2 |
| Total formula weight | 48788.05 |
| Authors | Papageorgiou, A.C. (deposition date: 2023-01-06, release date: 2023-05-24, Last modification date: 2024-06-19) |
| Primary citation | 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 Cited by 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: 37189361DOI: 10.3390/biom13040613 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.28 Å) |
Structure validation
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