C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Alpha subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. The class Alpha subfamily is composed of vertebrate GSTs which can form homodimer and heterodimers. There are at least six types of class Alpha GST subunits in rats, four of which have human counterparts, resulting in many possible isoenzymes with different activities, tissue distribution and substrate specificities. Human GSTA1-1 and GSTA2-2 show high GSH peroxidase activity. GSTA3-3 catalyzes the isomerization of intermediates in steroid hormone biosynthesis. GSTA4-4 preferentially catalyzes the GSH conjugation of alkenals.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608113   1 MYTEGMADLNEMILLLPLCRPEEKDAKIALIKEKTKSRYFPAFEKVLQSHGQDYLVGNKLSRADISLVELLYYVEELDSS 80
Cdd:cd03208     9 MYVEGTADLMEMIMMLPFLPPEEKEAKLALIKEKAKNRYFPVFEKVLKDHGQDFLVGNKLSRADVQLLEAILMVEELDPS 88

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2462608113  81 LISNFPLLKALKTRISNLPTVKKFLQPGSPRKPPADAKALEEARKIF 127
Cdd:cd03208    89 ILSDFPLLQAFKTRISNIPTIKKFLQPGSKRKPPPDEKYVETVRKVF 135

C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Alpha subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. The class Alpha subfamily is composed of vertebrate GSTs which can form homodimer and heterodimers. There are at least six types of class Alpha GST subunits in rats, four of which have human counterparts, resulting in many possible isoenzymes with different activities, tissue distribution and substrate specificities. Human GSTA1-1 and GSTA2-2 show high GSH peroxidase activity. GSTA3-3 catalyzes the isomerization of intermediates in steroid hormone biosynthesis. GSTA4-4 preferentially catalyzes the GSH conjugation of alkenals.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608113   1 MYTEGMADLNEMILLLPLCRPEEKDAKIALIKEKTKSRYFPAFEKVLQSHGQDYLVGNKLSRADISLVELLYYVEELDSS 80
Cdd:cd03208     9 MYVEGTADLMEMIMMLPFLPPEEKEAKLALIKEKAKNRYFPVFEKVLKDHGQDFLVGNKLSRADVQLLEAILMVEELDPS 88

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2462608113  81 LISNFPLLKALKTRISNLPTVKKFLQPGSPRKPPADAKALEEARKIF 127
Cdd:cd03208    89 ILSDFPLLQAFKTRISNIPTIKKFLQPGSKRKPPPDEKYVETVRKVF 135

glutathione s-transferase; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462608113  43 FEKVLQSHGQDYLVGNKLSRADISLVELLYYVEELDSSLISNFPLLKALKTRISNLPTVKKFL 105
Cdd:PTZ00057  135 FENILKKNHCNYFVGDNLTYADLAVFNLYDDIETKYPNSLKNFPLLKAHNEFISNLPNIKNYI 197

C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Alpha subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. The class Alpha subfamily is composed of vertebrate GSTs which can form homodimer and heterodimers. There are at least six types of class Alpha GST subunits in rats, four of which have human counterparts, resulting in many possible isoenzymes with different activities, tissue distribution and substrate specificities. Human GSTA1-1 and GSTA2-2 show high GSH peroxidase activity. GSTA3-3 catalyzes the isomerization of intermediates in steroid hormone biosynthesis. GSTA4-4 preferentially catalyzes the GSH conjugation of alkenals.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608113   1 MYTEGMADLNEMILLLPLCRPEEKDAKIALIKEKTKSRYFPAFEKVLQSHGQDYLVGNKLSRADISLVELLYYVEELDSS 80
Cdd:cd03208     9 MYVEGTADLMEMIMMLPFLPPEEKEAKLALIKEKAKNRYFPVFEKVLKDHGQDFLVGNKLSRADVQLLEAILMVEELDPS 88

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2462608113  81 LISNFPLLKALKTRISNLPTVKKFLQPGSPRKPPADAKALEEARKIF 127
Cdd:cd03208    89 ILSDFPLLQAFKTRISNIPTIKKFLQPGSKRKPPPDEKYVETVRKVF 135

Glutathione S-transferase, C-terminal domain; GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins in E. coli are also included in the alignment but are not known to have GST activity. The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain. In plants, GSTs are encoded by a large gene family (48 GST genes in Arabidopsis) and can be divided into the phi, tau, theta, zeta, and lambda classes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608113   7 ADLNEMILLLPLCRPEEKDAKIALIKEKTKSRYFPAFEKVLQshGQDYLVGNKLSRADISLVELLYYVEELD-SSLISNF 85
Cdd:pfam00043   2 MDLRMQIALLPYVPPEEKKEPEVDEALEKVARVLSALEEVLK--GQTYLVGDKLTLADIALAPALLWLYELDpACLREKF 79

                          90
                  ....*....|....
gi 2462608113  86 PLLKALKTRISNLP 99
Cdd:pfam00043  80 PNLKAWFERVAARP 93

C-terminal, alpha helical domain of Class Pi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Pi subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. Class Pi GST is a homodimeric eukaryotic protein. The human GSTP1 is mainly found in erythrocytes, kidney, placenta and fetal liver. It is involved in stress responses and in cellular proliferation pathways as an inhibitor of JNK (c-Jun N-terminal kinase). Following oxidative stress, monomeric GSTP1 dissociates from JNK and dimerizes, losing its ability to bind JNK and causing an increase in JNK activity, thereby promoting apoptosis. GSTP1 is expressed in various tumors and is the predominant GST in a wide range of cancer cells. It has been implicated in the development of multidrug-resistant tumors.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462608113  43 FEKVLQSH-GQDYLVGNKLSRADISLVELLYYVEELDSSLISNFPLLKALKTRISNLPTVKKFLQPGSPRKPP 114
Cdd:cd03210    47 FEKLLAKNnGKGFIVGDKISFADYNLFDLLDIHLVLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNRP 119

Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462608113  20 RPEEKDAKIALIKEKTKsRYFPAFEKVLQshGQDYLVGNKLSRADISLVELLYYVEELDSSLiSNFPLLKALKTRISNLP 99
Cdd:COG0625   116 APEKDPAAIARARAELA-RLLAVLEARLA--GGPYLAGDRFSIADIALAPVLRRLDRLGLDL-ADYPNLAAWLARLAARP 191

                          90
                  ....*....|.
gi 2462608113 100 TVKKFLQPGSP 110
Cdd:COG0625   192 AFQRALAAAEP 202

C-terminal, alpha helical domain of fungal Ure2p Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Ure2p subfamily; composed of the Saccharomyces cerevisiae Ure2p and related fungal proteins. Ure2p is a regulator for nitrogen catabolism in yeast. It represses the expression of several gene products involved in the use of poor nitrogen sources when rich sources are available. A transmissible conformational change of Ure2p results in a prion called [Ure3], an inactive, self-propagating and infectious amyloid. Ure2p displays a GST fold containing an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The N-terminal thioredoxin-fold domain is sufficient to induce the [Ure3] phenotype and is also called the prion domain of Ure2p. In addition to its role in nitrogen regulation, Ure2p confers protection to cells against heavy metal ion and oxidant toxicity, and shows glutathione (GSH) peroxidase activity. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of GSH with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462608113  44 EKVLQSHGQDYLVGNKLSRADISLVELLYYVE----ELDSSLISNFPLLKALKTRISNLPTVKK 103
Cdd:cd10293    53 ETALAERYRVWLVGDKFTIADLAFVPWNNVVDmifiDPELDIKKEFPHVYKWLKRMLARPAVKK 116

C-terminal, alpha helical domain of Ure2p and related Glutathione S-transferase-like proteins; Glutathione S-transferase (GST) C-terminal domain family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p, YfcG and YghU from Escherichia coli, and related GST-like proteins. Ure2p is a regulator for nitrogen catabolism in yeast. It represses the expression of several gene products involved in the use of poor nitrogen sources when rich sources are available. A transmissible conformational change of Ure2p results in a prion called [Ure3], an inactive, self-propagating and infectious amyloid. Ure2p displays a GST fold containing an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The N-terminal thioredoxin-fold domain is sufficient to induce the [Ure3] phenotype and is also called the prion domain of Ure2p. In addition to its role in nitrogen regulation, Ure2p confers protection to cells against heavy metal ion and oxidant toxicity, and shows glutathione (GSH) peroxidase activity. YfcG and YghU are two of the nine GST homologs in the genome of Escherichia coli. They display very low or no GSH transferase, but show very good disulfide bond oxidoreductase activity. YghU also shows modest organic hydroperoxide reductase activity. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of GSH with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462608113  45 KVLQSH--GQDYLVGNKLSRADISLVELLYYVEELDSSLISNFPLLKALKTRISNLPTVKK 103
Cdd:cd03178    50 GVLDKRlsDRPYLAGEEYSIADIALYPWTHYADLGGFADLSEYPNVKRWLERIAARPAVQK 110

C-terminal, alpha helical domain of the Glutathione S-transferase family; Glutathione S-transferase (GST) family, C-terminal alpha helical domain; a large, diverse group of cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. In addition, GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. This family, also referred to as soluble GSTs, is the largest family of GSH transferases and is only distantly related to the mitochondrial GSTs (GSTK). Soluble GSTs bear no structural similarity to microsomal GSTs (MAPEG family) and display additional activities unique to their group, such as catalyzing thiolysis, reduction and isomerization of certain compounds. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. Based on sequence similarity, different classes of GSTs have been identified, which display varying tissue distribution, substrate specificities and additional specific activities. In humans, GSTs display polymorphisms which may influence individual susceptibility to diseases such as cancer, arthritis, allergy and sclerosis. Some GST family members with non-GST functions include glutaredoxin 2, the CLIC subfamily of anion channels, prion protein Ure2p, crystallins, metaxins, stringent starvation protein A, and aminoacyl-tRNA synthetases.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462608113  42 AFEKVLQshGQDYLVGNKLSRADISLVELLYYVEELD--SSLISNFPLLKALKTRI 95
Cdd:cd00299    47 ALEQLLA--GRPYLAGDQFSLADVALAPVLARLEALGpyYDLLDEYPRLKAWYDRL 100