8C5D | pdb_00008c5d

Glutathione transferase P1-1 from Mus musculus

PDB DOI: https://doi.org/10.2210/pdb8C5D/pdb

Classification: TRANSFERASE
Organism(s): Mus musculus
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2023-01-06 Released: 2023-05-24
Deposition Author(s): Papageorgiou, A.C.
Funding Organization(s): iNEXT

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.28 Å
R-Value Free:
0.200 (Depositor), 0.200 (DCC)
R-Value Work:
0.175 (Depositor), 0.170 (DCC)
R-Value Observed:
0.176 (Depositor)

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

Inhibition Analysis and High-Resolution Crystal Structure of Mus musculus Glutathione Transferase P1-1.

Kupreienko, O., Pouliou, F., Konstandinidis, K., Axarli, I., Douni, E., Papageorgiou, A.C., Labrou, N.E.

(2023) Biomolecules 13

PubMed: 37189361 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.3390/biom13040613
Primary Citation of Related Structures:
8C5D

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 Mus musculus ( Mm 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 ₅₀ = 11.3 ± 0.5 μΜ) towards Mm 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 Mm 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 Mm 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 Mm GSTP1-1 and provide a new compound as a potential lead structure for future drug/inhibitor development.

Organizational Affiliation

Laboratory of Enzyme Technology, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 75 Iera Odos Street, 11855 Athens, Greece.

Macromolecule Content

Total Structure Weight: 48.79 kDa
Atom Count: 4,028
Modeled Residue Count: 418
Deposited Residue Count: 420
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Glutathione S-transferase P 1	A, B	210	Mus musculus	Mutation(s): 0 Gene Names: Gstp1, Gstpib EC: 2.5.1.18
UniProt
Find proteins for P19157 (Mus musculus) Explore P19157 Go to UniProtKB: P19157
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P19157
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
GTB (Subject of Investigation/LOI) Query on GTB Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain O [auth B] MOL2 format, chain D [auth A] MOL2 format, chain O [auth B] mmCIF format, chain D [auth A] mmCIF format, chain O [auth B]	D [auth A], O [auth B]	S-(P-NITROBENZYL)GLUTATHIONE C₁₇ H₂₂ N₄ O₈ S OAWORKDPTSAMBZ-STQMWFEESA-N		Interactions Focus chain D [auth A] Focus chain O [auth B] Interactions & Density Focus chain D [auth A] Focus chain O [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain N [auth B] MOL2 format, chain C [auth A] MOL2 format, chain N [auth B] mmCIF format, chain C [auth A] mmCIF format, chain N [auth B]	C [auth A], N [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain N [auth B] Interactions & Density Focus chain C [auth A] Focus chain N [auth B]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain K [auth A] SDF format, chain L [auth A] SDF format, chain T [auth B] SDF format, chain U [auth B] MOL2 format, chain K [auth A] MOL2 format, chain L [auth A] MOL2 format, chain T [auth B] MOL2 format, chain U [auth B] mmCIF format, chain K [auth A] mmCIF format, chain L [auth A] mmCIF format, chain T [auth B] mmCIF format, chain U [auth B]	K [auth A], L [auth A], T [auth B], U [auth B]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain K [auth A] Focus chain L [auth A] Focus chain T [auth B] Focus chain U [auth B] Interactions & Density Focus chain K [auth A] Focus chain L [auth A] Focus chain T [auth B] Focus chain U [auth B]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain M [auth A] MOL2 format, chain M [auth A] mmCIF format, chain M [auth A]	M [auth A]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain M [auth A] Interactions & Density Focus chain M [auth A]
NA Query on NA Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain J [auth A] SDF format, chain P [auth B] SDF format, chain Q [auth B] SDF format, chain R [auth B] SDF format, chain S [auth B] SDF format, chain V [auth B] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] MOL2 format, chain P [auth B] MOL2 format, chain Q [auth B] MOL2 format, chain R [auth B] MOL2 format, chain S [auth B] MOL2 format, chain V [auth B] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A] mmCIF format, chain P [auth B] mmCIF format, chain Q [auth B] mmCIF format, chain R [auth B] mmCIF format, chain S [auth B] mmCIF format, chain V [auth B]	E [auth A] F [auth A] G [auth A] H [auth A] I [auth A] E [auth A], F [auth A], G [auth A], H [auth A], I [auth A], J [auth A], P [auth B], Q [auth B], R [auth B], S [auth B], V [auth B]	SODIUM ION Na FKNQFGJONOIPTF-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain P [auth B] Focus chain Q [auth B] Focus chain R [auth B] Focus chain S [auth B] Focus chain V [auth B] Interactions & Density Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain P [auth B] Focus chain Q [auth B] Focus chain R [auth B] Focus chain S [auth B] Focus chain V [auth B]