5JCU

Crystal Structure of hGSTA1-1 with Glutathione Adduct of Phenethyl Isothiocyanate and Cystein Adduct of Phenethyl Isothiocyanate

PDB DOI: https://doi.org/10.2210/pdb5JCU/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2016-04-15 Released: 2016-10-12
Deposition Author(s): Kumari, V., Ji, X.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.93 Å
R-Value Free: 0.240
R-Value Work: 0.177
R-Value Observed: 0.178

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

Irreversible Inhibition of Glutathione S-Transferase by Phenethyl Isothiocyanate (PEITC), a Dietary Cancer Chemopreventive Phytochemical.

Kumari, V., Dyba, M.A., Holland, R.J., Liang, Y.H., Singh, S.V., Ji, X.

(2016) PLoS One 11: e0163821-e0163821

PubMed: 27684484 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1371/journal.pone.0163821
Primary Citation of Related Structures:
5JCU, 5JCW

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.

Organizational Affiliation

Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.

Macromolecule Content

Total Structure Weight: 105.06 kDa
Atom Count: 8,537
Modelled Residue Count: 884
Deposited Residue Count: 884
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Glutathione S-transferase A1	A, B, C, D	221	Homo sapiens	Mutation(s): 0 Gene Names: GSTA1 EC: 2.5.1.18
UniProt & NIH Common Fund Data Resources
Find proteins for P08263 (Homo sapiens) Explore P08263 Go to UniProtKB: P08263
PHAROS: P08263 GTEx: ENSG00000243955
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P08263
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
GVX Query on GVX Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain I [auth B] SDF format, chain L [auth C] SDF format, chain M [auth D] MOL2 format, chain E [auth A] MOL2 format, chain I [auth B] MOL2 format, chain L [auth C] MOL2 format, chain M [auth D]	E [auth A], I [auth B], L [auth C], M [auth D]	L-gamma-glutamyl-S-[(2-phenylethyl)carbamothioyl]-L-cysteinylglycine C₁₉ H₂₆ N₄ O₆ S₂ WSGBVCNCZSZCGE-KBPBESRZSA-N		Interactions Focus chain E [auth A] Focus chain I [auth B] Focus chain L [auth C] Focus chain M [auth D] Interactions & Density Focus chain E [auth A] Focus chain I [auth B] Focus chain L [auth C] Focus chain M [auth D]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain J [auth C] SDF format, chain K [auth C] SDF format, chain N [auth D] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain J [auth C] MOL2 format, chain K [auth C] MOL2 format, chain N [auth D]	F [auth A] G [auth A] H [auth A] J [auth C] K [auth C] F [auth A], G [auth A], H [auth A], J [auth C], K [auth C], N [auth D]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain J [auth C] Focus chain K [auth C] Focus chain N [auth D] Interactions & Density Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain J [auth C] Focus chain K [auth C] Focus chain N [auth D]

Modified Residues 1 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
6M6 Query on 6M6	A, B, C, D	L-PEPTIDE LINKING	C₁₂ H₁₆ N₂ O₂ S₂		CYS

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.93 Å
R-Value Free: 0.240
R-Value Work: 0.177
R-Value Observed: 0.178
Space Group: C 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 100.335	α = 90
b = 92.666	β = 92.18
c = 104.051	γ = 90

Software Package:

Software Name	Purpose
PHENIX	refinement
DENZO	data reduction
SCALEPACK	data scaling
PHENIX	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2016-10-12

Deposition Author(s):

Kumari, V.

Ji, X.

Revision History (Full details and data files)

Version 1.0: 2016-10-12
Type: Initial release
Version 1.1: 2023-08-30
Changes: Data collection, Database references, Derived calculations, Structure summary
Version 1.2: 2023-09-27
Changes: Refinement description