DB code: D00524

CATH domain 3.40.30.10 : Glutaredoxin Catalytic domain
1.20.1050.10 : Glutathione S-transferase Yfyf (Class Pi); Chain A, domain 2
E.C. 2.5.1.18 1.11.1.9
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P30711 Glutathione S-transferase theta-1
EC 2.5.1.18
GST class-theta-1
Glutathione transferase T1-1
NP_000844.2 (Protein)
NM_000853.2 (DNA/RNA sequence)
PF00043 (GST_C)
PF02798 (GST_N)
[Graphical View]
P0CG30 Glutathione S-transferase theta-2B
EC 2.5.1.18
GST class-theta-2
Glutathione S-transferase theta-2
NP_000845.1 (Protein)
NM_000854.3 (DNA/RNA sequence)
NP_001074312.1 (Protein)
NM_001080843.2 (DNA/RNA sequence)
PF00043 (GST_C)
PF02798 (GST_N)
[Graphical View]
P0CG29 Glutathione S-transferase theta-2
EC 2.5.1.18
GST class-theta-2
PF00043 (GST_C)
PF02798 (GST_N)
[Graphical View]

KEGG enzyme name
Glutathione transferase
(EC 2.5.1.18 )
Glutathione S-transferase
(EC 2.5.1.18 )
Glutathione S-alkyltransferase
(EC 2.5.1.18 )
Glutathione S-aryltransferase
(EC 2.5.1.18 )
S-(Hydroxylalkyl)-glutathione liase
(EC 2.5.1.18 )
Glutathione S-aralkyltransferase
(EC 2.5.1.18 )
Glutathione peroxidase
(EC 1.11.1.9 )
GSH peroxidase
(EC 1.11.1.9 )
Selenium-glutathione peroxidase
(EC 1.11.1.9 )
Reduced glutathione peroxidase
(EC 1.11.1.9 )

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P30711 GSTT1_HUMAN RX + glutathione = HX + R-S-glutathione. Homodimer. Cytoplasm.
P0CG30 GSTT2_HUMAN RX + glutathione = HX + R-S-glutathione. Homodimer. Cytoplasm.
P0CG29 GST2_HUMAN RX + glutathione = HX + R-S-glutathione. Homodimer. Cytoplasm.

KEGG Pathways
Map code Pathways E.C.
MAP00480 Glutathione metabolism (2.5.1.18, 1.11.1.9)
MAP00980 Metabolism of xenobiotics by cytochrome P450 2.5.1.18
MAP00982 Drug metabolism - cytochrome P450 2.5.1.18
MAP00590 Arachidonic acid metabolism 1.11.1.9

Compound table
Substrates Products Intermediates
KEGG-id C01322 C00051 C16738 L00111 C00722 C01372 C15498 C01318 C02320 C00059 L00112 L00113 L00114 C01335 C00127 C00001
E.C. 2.5.1.18
(2.5.1.18, 1.11.1.9)
2.5.1.18
2.5.1.18
2.5.1.18
2.5.1.18
1.11.1.9
2.5.1.18
2.5.1.18
2.5.1.18
2.5.1.18
2.5.1.18
2.5.1.18
1.11.1.9
1.11.1.9
1.11.1.9
Compound RX Glutathione Sulfuric monoester 1-menaphthyl sulfate Epoxide Alkene ROOH HX R-S-Glutathione sulfate 1-menaphthyl glutathione Glutathione-conjugated alcohol Glutathione-conjugated compound ROH Glutathione disulfide Water
Type halide amino acids,carboxyl group,peptide/protein,sulfhydryl group sulfate group aromatic ring (only carbon atom),sulfate group carbohydrate lipid others halide amide group,carboxyl group,peptide/protein,sulfide group sulfate group amide group,aromatic ring (only carbon atom),carboxyl group,peptide/protein,sulfide group amide group,carbohydrate,carboxyl group,peptide/protein,sulfide group amide group,carboxyl group,peptide/protein,sulfide group carbohydrate amino acids,carboxyl group,peptide/protein,disulfide bond H2O
ChEBI 16856
26836
17858
15377
PubChem 124886
25246407
33524
1118
22066174
5152822
449471
11215652
65359
22247451
962
2c3nA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3nB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3nC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3nD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3qA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:GTX Unbound Unbound Unbound Unbound Unbound Unbound
2c3qB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:GTX Unbound Unbound Unbound Unbound Unbound Unbound
2c3qC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:GTX Unbound Unbound Unbound Unbound Unbound Unbound
2c3qD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:GTX Unbound Unbound Unbound Unbound Unbound Unbound
2c3tA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3tB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3tC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3tD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ljrA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:GSH Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ljrB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:GSH Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2ljrA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2ljrB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3ljrA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:GGC Unbound Unbound Unbound Unbound
3ljrB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:GGC Unbound Unbound Unbound Unbound
4mpgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:GSH Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
4mpgB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:GSH Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
4mpfA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
4mpfB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3nA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:IOD Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3nB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:IOD Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3nC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:IOD Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3nD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:IOD Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3qA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:IOD Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3qB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:IOD Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3qC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:IOD Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3qD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:IOD Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3tA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3tB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3tC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c3tD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ljrA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ljrB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2ljrA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2ljrB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3ljrA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:SO4 Unbound Unbound Unbound Unbound Unbound
3ljrB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:SO4 Unbound Unbound Unbound Unbound Unbound
4mpgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
4mpgB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:UNL Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
4mpfA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Analogue:PO4 Unbound Unbound Unbound Unbound Unbound
4mpfB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Analogue:PO4 Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [1] and [6]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
2c3nA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
2c3nB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
2c3nC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
2c3nD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
2c3qA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
2c3qB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
2c3qC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
2c3qD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
2c3tA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
2c3tB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
2c3tC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
2c3tD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
1ljrA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
1ljrB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
2ljrA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
2ljrB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
3ljrA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
3ljrB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
4mpgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
4mpgB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
4mpfA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
4mpfB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 11
2c3nA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107
2c3nB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107
2c3nC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107
2c3nD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107
2c3qA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107 mutant W234R
2c3qB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107 mutant W234R
2c3qC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107 mutant W234R
2c3qD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107 mutant W234R
2c3tA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107 mutant W234R
2c3tB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107 mutant W234R
2c3tC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107 mutant W234R
2c3tD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107 mutant W234R
1ljrA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107
1ljrB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107
2ljrA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107
2ljrB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107
3ljrA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107
3ljrB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107
4mpgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107
4mpgB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107
4mpfA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107
4mpfB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 107

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[6]
p.317-318
[7]
Fig.1
[9]
p.249-253
[14]

References
[1]
Resource
Comments
Medline ID
PubMed ID 7575461
Journal Biochem J
Year 1995
Volume 311
Pages 247-50
Authors Board PG, Coggan M, Wilce MC, Parker MW
Title Evidence for an essential serine residue in the active site of the Theta class glutathione transferases.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8870684
Journal Biochem J
Year 1996
Volume 319
Pages 315-21
Authors Tan KL, Chelvanayagam G, Parker MW, Board PG
Title Mutagenesis of the active site of the human Theta-class glutathione transferase GSTT2-2: catalysis with different substrates involves different residues.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9074797
Journal Chem Res Toxicol
Year 1997
Volume 10
Pages 2-18
Authors Armstrong RN
Title Structure, catalytic mechanism, and evolution of the glutathione transferases.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9307035
Journal Biochem J
Year 1997
Volume 326
Pages 837-46
Authors Sherratt PJ, Pulford DJ, Harrison DJ, Green T, Hayes JD
Title Evidence that human class Theta glutathione S-transferase T1-1 can catalyse the activation of dichloromethane, a liver and lung carcinogen in the mouse. Comparison of the tissue distribution of GST T1-1 with that of classes Alpha, Mu and Pi GST in human.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9434735
Journal Arch Biochem Biophys
Year 1997
Volume 348
Pages 247-54
Authors Jemth P, Mannervik B
Title Kinetic characterization of recombinant human glutathione transferase T1-1, a polymorphic detoxication enzyme.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS).
Medline ID
PubMed ID 9551553
Journal Structure
Year 1998
Volume 6
Pages 309-22
Authors Rossjohn J, McKinstry WJ, Oakley AJ, Verger D, Flanagan J, Chelvanayagam G, Tan KL, Board PG, Parker MW
Title Human theta class glutathione transferase: the crystal structure reveals a sulfate-binding pocket within a buried active site.
Related PDB 1ljr 2ljr 3ljr
Related UniProtKB P0CG30
[7]
Resource
Comments
Medline ID
PubMed ID 10190541
Journal Chem Biol Interact
Year 1999
Volume 117
Pages 1-14
Authors Bogaards JJ, Venekamp JC, Salmon FG, van Bladeren PJ
Title Conjugation of isoprene monoepoxides with glutathione, catalyzed by alpha, mu, pi and theta-class glutathione S-transferases of rat and man.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10548067
Journal Protein Sci
Year 1999
Volume 8
Pages 2205-12
Authors Flanagan JU, Rossjohn J, Parker MW, Board PG, Chelvanayagam G
Title Mutagenic analysis of conserved arginine residues in and around the novel sulfate binding pocket of the human Theta class glutathione transferase T2-2.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 11018744
Journal Mutat Res
Year 2000
Volume 463
Pages 247-83
Authors Landi S
Title Mammalian class theta GST and differential susceptibility to carcinogens: a review.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 12054768
Journal J Mol Biol
Year 2002
Volume 318
Pages 59-70
Authors Broo K, Larsson AK, Jemth P, Mannervik B
Title An ensemble of theta class glutathione transferases with novel catalytic properties generated by stochastic recombination of fragments of two mammalian enzymes.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 11884241
Journal Toxicol Appl Pharmacol
Year 2002
Volume 179
Pages 89-97
Authors Sherratt PJ, Williams S, Foster J, Kernohan N, Green T, Hayes JD
Title Direct comparison of the nature of mouse and human GST T1-1 and the implications on dichloromethane carcinogenicity.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 14615977
Journal Chem Res Toxicol
Year 2003
Volume 16
Pages 1493-9
Authors Guengerich FP, McCormick WA, Wheeler JB
Title Analysis of the kinetic mechanism of haloalkane conjugation by mammalian theta-class glutathione transferases.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 12588193
Journal Chem Res Toxicol
Year 2003
Volume 16
Pages 216-26
Authors Ross MK, Pegram RA
Title Glutathione transferase theta 1-1-dependent metabolism of the water disinfection byproduct bromodichloromethane.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 12542971
Journal J Biochem Mol Biol
Year 2003
Volume 36
Pages 20-7
Authors Guengerich FP
Title Activation of dihaloalkanes by thiol-dependent mechanisms.
Related PDB
Related UniProtKB
[15]
Resource
Comments X-RAY CRYSTALLOGRAPHY.
Medline ID
PubMed ID 16298388
Journal J Mol Biol
Year 2006
Volume 355
Pages 96-105
Authors Tars K, Larsson AK, Shokeer A, Olin B, Mannervik B, Kleywegt GJ
Title Structural basis of the suppressed catalytic activity of wild-type human glutathione transferase T1-1 compared to its W234R mutant.
Related PDB 2c3n 2c3t 2c3q
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 17011574
Journal J Mol Biol
Year 2006
Volume 364
Pages 400-10
Authors Griswold KE, Aiyappan NS, Iverson BL, Georgiou G
Title The evolution of catalytic efficiency and substrate promiscuity in human theta class 1-1 glutathione transferase.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 19664997
Journal Arch Biochem Biophys
Year 2009
Volume 490
Pages 24-9
Authors Josephy PD, Kent M, Mannervik B
Title Single-nucleotide polymorphic variants of human glutathione transferase T1-1 differ in stability and functional properties.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 20097269
Journal Biochim Biophys Acta
Year 2010
Volume 1800
Pages 466-73
Authors Shokeer A, Mannervik B
Title Residue 234 is a master switch of the alternative-substrate activity profile of human and rodent theta class glutathione transferase T1-1.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 24756107
Journal PLoS Biol
Year 2014
Volume 12
Pages e1001843
Authors Mashiyama ST, Malabanan MM, Akiva E, Bhosle R, Branch MC, Hillerich B, Jagessar K, Kim J, Patskovsky Y, Seidel RD, Stead M, Toro R, Vetting MW, Almo SC, Armstrong RN, Babbitt PC
Title Large-scale determination of sequence, structure, and function relationships in cytosolic glutathione transferases across the biosphere.
Related PDB
Related UniProtKB

Comments
Cytosolic glutathione transferases (GSTs), with EC number 2.5.1.18, comprise a large superfamily, to which this enzyme belongs (see [3], [19]). cytosolic GSTs catalyze various reactions, such as nucleophilic substitution, nucleophilic addition, epoxide ring opening, isomerization, hydrolytic dehalogenation, disulfide reductase, peroxidase, thiocyanate reductase, reductive dehalogenation, deglutathionylation (see [19]). These reactions can be classified into three categories: (1) reactions where glutathione (GSH) is consumed, (2) reactions where GSH is not consumed, and (3) reactions where two GSH molecules are oxidized to produce GSSG (see [19]).
In addition to this superfamily, there are three more GST families with EC 2.5.1.18: (a) cytosolic GST kappa class with a thioredoxin domain (CATH 3.40.30.10), (b) membrane-bound GSTs (CATH 1.20.120.50), and (c) metal-dependent GST, which is called fosfomycin resistance protein (CATH 3.10.180.10) (see [3], [19]).
This enzyme class, the human theta class glutathione transferase (GST), is the most ancient class among other GSTs (see [9]).This enzyme class has a sulfatase activity and a halogenase activity, unlike the other classes of the homologous enzymes (GSTs), alpha, mu, pi and sigma (see [2], [6], [8] and [9]). In contrast, theta class enzyme lacks activity toward the model substrate, 1-chloro-2,4-dinitrobenzene (CDNB), compared to the other classes of GSTs (see [2], [8] and [9]).
In the sulfatase reaction for this enzyme class, 1-menaphthyl sulphate (MSu)(L00111) reacts with glutathione (C00051), giving rise to 1-menaphthyl glutathione conjugate (L00112) and sulfate (C00059) (see [2], [8], [9]). However, this reaction does not involve any water molecule, which is essential in hydrolysis of sulfatase reaction. Consequently, this reaction is similar to transfer reaction, in which sulfate is a leaving group instead of other substances such as halide ion. Thus, these reactions are classified as nucleophilic substitution (see [19]).
RX + Glutathione => HX + R-S-Glutathione; nucleophilic substitution for ordinary GST reaction;
MSu(L00111) + Glutathione => sulfate + 1-menaphthyl-glutathione(L00112); theta GST reaction
or
Sulfuric monoester(C16738) + Glutathione => sulfate + R-S-Glutathione; theta GST reaction
According to the literature [8], the interaction between Arg107 and the sulfate group of MSu (L00111) will lead to the the positive charge increases on the methyl carbon of MSu, giving rise to the carbonium cation. The thiolate group of glutathione may make a nucleophilic attack on the carbonium cation, to produce 1-menaphthyl glutathione and free sulfate (see [8]).
Human GSTT1-1 shows suppressed catalytic activity, due to Trp234 that is occupying a significant portion of the active site, compared to the counterpart enzyme, GSTT1-1, from mouse (see [15]). In contrast to the wild type, Trp234Arg mutant shows an enhanced activity, probably because Arg234 interacts with the carboxylate group of glutathione (see [15]).
In addition to these transfer reactions, this enzyme can catalyze the following reactions (see [19]):
Epoxide ring opening; Epoxide + Glutathione => Glutathione-conjucated alcohol(L00113)
Conjugate addition; Alkene + Glutathione => Glutathione-conjugated compound(L00114)
Peroxidase reaction; 2 x Glutathione + ROOH(hydroperoxide) => ROH + glutathione disulfide + H2O
Here, epoxide ring opening may be classified into intramolecular transfer reaction.
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For GSTT1-1, the following substances can be substrates: dichloromethane (DCM), ethylene-dibromide (EDB), p-nitrobenzyl chloride (PNBC), p-nitrophenethyl bromide (PNPB), methyl chloride (MeC), methyl iodide (MeI), and various halogenated methanes and ethanes, 1,2-epoxy-3-(p-nitro-phenoxy)propane (EPNPP) and the isoprene monoepoxides 3,4 epoxy-3-methyl-1-butene (EPOX-I) and 3,4-epoxy-2-methyl-1-butene (EPOX-II). In addition, ethylene epoxide (EO) and 1,3-butadiene derivatives such as the 3,4-epoxybutene (MEB), and the 1,2,3,4-diepoxybutane (DEB) are highly suspected substrates for GSTT1-1 (see [9])
GSTT1-1 also shows a peroxidase activity towards phospholipid hydroperoxides, cumene hydroperoxide and t-butyl hydroperoxide, but not towards a range of secondary lipid-peroxidation products, such as the trans-alk-2-enals and trans,trans-alka-2,4-dienals (see [9]).
GSTT2-2, in contrast to GSTT1-1, shows a significant activity against most lipid peroxidation products or the polycyclic aromatic hydrocarbon (PAH) 5-hydroxy-methylchrysene and the food-derivative mutagen N-acetoxy-PhIP, although no activity was shown towards steroid hydroperoxides, EPNPP, and PNBC (see [9]).
GSTT2-2, but not GSTT1-1, also shows a sulfatase activity towards the menaphthyl sulfate [12] and the 1-methyl-sulfate (see [9]).

Created Updated
2009-02-04 2015-04-24