C-terminal, alpha helical domain of Stringent starvation protein A; Glutathione S-transferase (GST) C-terminal domain family, Stringent starvation protein A (SspA) subfamily; SspA is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation. SspA adopts the GST fold with an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, but it does not bind glutathione (GSH) and lacks GST activity. SspA is highly conserved among gram-negative bacteria. Related proteins found in Neisseria (called RegF), Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835513776  93 PVARGESRLYMHRIEKDWYSLMEVIM-SSSGAQADNARRQLREELMQIAPVFGQKPYFLSDEFSLVDCYLAPLLWRLPIL 171
Cdd:cd03186     1 PVSRARSRLMMHRIEQDWYPLLDTILnGRDEKEAEKARKELRESLTALAPVFAASPYFLSEEFSLVDCYLAPLLWRLPAL 80

                          90       100
                  ....*....|....*....|....*....
gi 1835513776 172 GIELSGaGSKELKGYMTRVFERDSFLASL 200
Cdd:cd03186    81 GIELPK-QAKAIKDYMERVFARDSFQASL 108

Glutathione S-transferase, N-terminal domain; Function: conjugation of reduced glutathione to a variety of targets. Also included in the alignment, but not GSTs: S-crystallins from squid (similarity to GST previously noted); eukaryotic elongation factors 1-gamma (not known to have GST activity and similarity not previously recognized); HSP26 family of stress-related proteins including auxin-regulated proteins in plants and stringent starvation proteins in E. coli (not known to have GST activity and similarity not previously recognized). The glutathione molecule binds in a cleft between the N- and C-terminal domains - the catalytically important residues are proposed to reside in the N-terminal domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1835513776   9 SVMTLFSGPVDIYSHQVRIVLAEKGVSFEIEHVEKDNPPQ---DLIDLNPNQSVPTLVDRELTLWESRIIMEYLDE 81
Cdd:pfam02798   1 MVLTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEkspELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

C-terminal, alpha helical domain of Stringent starvation protein A; Glutathione S-transferase (GST) C-terminal domain family, Stringent starvation protein A (SspA) subfamily; SspA is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation. SspA adopts the GST fold with an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, but it does not bind glutathione (GSH) and lacks GST activity. SspA is highly conserved among gram-negative bacteria. Related proteins found in Neisseria (called RegF), Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835513776  93 PVARGESRLYMHRIEKDWYSLMEVIM-SSSGAQADNARRQLREELMQIAPVFGQKPYFLSDEFSLVDCYLAPLLWRLPIL 171
Cdd:cd03186     1 PVSRARSRLMMHRIEQDWYPLLDTILnGRDEKEAEKARKELRESLTALAPVFAASPYFLSEEFSLVDCYLAPLLWRLPAL 80

                          90       100
                  ....*....|....*....|....*....
gi 1835513776 172 GIELSGaGSKELKGYMTRVFERDSFLASL 200
Cdd:cd03186    81 GIELPK-QAKAIKDYMERVFARDSFQASL 108

GST_N family, Stringent starvation protein A (SspA) subfamily; SspA is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation. SspA adopts the GST fold with an N-terminal TRX-fold domain and a C-terminal alpha helical domain, but it does not bind glutathione (GSH) and lacks GST activity. SspA is highly conserved among gram-negative bacteria. Related proteins found in Neisseria (called RegF), Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1835513776  11 MTLFSGPVDIYSHQVRIVLAEKGVSFEIEHVEKDNPPQDLIDLNPNQSVPTLVDRELTLWESRIIMEYLDERF 83
Cdd:cd03059     1 MTLYSGPDDVYSHRVRIVLAEKGVSVEIIDVDPDNPPEDLAELNPYGTVPTLVDRDLVLYESRIIMEYLDERF 73

Glutathione S-transferase (GST) family, N-terminal 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 subfamily, a member of the DsbA family). 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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, metaxin 2 and stringent starvation protein A.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1835513776  11 MTLFSGPVDIYSHQVRIVLAEKGVSFEIEHVEKDNPPQ-DLIDLNPNQSVPTLVDRELTLWESRIIMEYLD 80
Cdd:cd00570     1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQeEFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

maleylacetoacetate isomerase; Maleylacetoacetate isomerase is an enzyme of tyrosine and phenylalanine catabolism. It requires glutathione and belongs by homology to the zeta family of glutathione S-transferases. The enzyme (EC 5.2.1.2) is described as active also on maleylpyruvate, and the example from a Ralstonia sp. catabolic plasmid is described as a maleylpyruvate isomerase involved in gentisate catabolism. [Energy metabolism, Amino acids and amines]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835513776  22 SHQVRIVLAEKGVSFEIEHV----EKDNPPQDLIDLNPNQSVPTLVDRELTLWESRIIMEYLDERFPHPPLMPVYPVARG 97
Cdd:TIGR01262  11 SYRVRIALALKGIDYEYVPVnllrDGEQRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETYPDPPLLPADPIKRA 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835513776  98 ESRLYMHRIEKDWYSL-----MEVIMSSSGAQADNARRQLR----------EELMQiaPVFGQkpYFLSDEFSLVDCYLA 162
Cdd:TIGR01262  91 RVRALALLIACDIHPLnnlrvLQYLREKLGVEEEARNRWYQhwiskgfaalEALLQ--PHAGR--FCVGDTPTLADLCLV 166

                         170
                  ....*....|....*
gi 1835513776 163 PLLWRLPILGIELSG 177
Cdd:TIGR01262 167 PQVYNAERFGVDLTP 181

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1835513776  13 LFSGPVDIYSHQVRIVLAEKGVSFEIEHVEKDNPPQDLIDLNPNQSVPTLVDRELTLWESRIIMEYLDERFPHPP 87
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIPPGDHPPELLAKNPLGKVPVLEDDGGILCESLAIIDYLEELYPGPP 75

glutathione transferase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835513776  21 YSHQVRIVLAEKGVSFEIEHV---EKDNPPQDLIDLNPNQSVPTLVDRELTLWESRIIMEYLDERFPHPPLMPVYPV--- 94
Cdd:PRK15113   18 YVMSAFVALQEKGLPFELKTVdldAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEERFAPPAWERIYPAdlq 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835513776  95 ARGESRLYMHRIEKDwysLM--------EVIMS-------SSGAQADNARrqlreeLMQIAP-VFGQKPYFLSDEFSLVD 158
Cdd:PRK15113   98 ARARARQIQAWLRSD---LMplreerptDVVFAgakkaplSEAGKAAAEK------LFAVAErLLAPGQPNLFGEWCIAD 168

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1835513776 159 CYLAPLLWRLPILGIELSGAgskeLKGYMTRVFERDS 195
Cdd:PRK15113  169 TDLALMLNRLVLHGDEVPER----LADYATFQWQRAS 201

GST_N family, unknown subfamily 3; composed of uncharacterized bacterial proteins with similarity to GSTs. 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. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1835513776  11 MTLFSGPVDIYSHQVRIVLAEKG--VSFEIEHVEKDNPPQDLIDLNPNQSVPTLV-DRELTLWESRIIMEYLD 80
Cdd:cd03049     1 MKLLYSPTSPYVRKVRVAAHETGlgDDVELVLVNPWSDDESLLAVNPLGKIPALVlDDGEALFDSRVICEYLD 73

GST_N family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p and related GSTs. 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The N-terminal TRX-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. Characterized GSTs in this subfamily include Aspergillus fumigatus GSTs 1 and 2, and Schizosaccharomyces pombe GST-I. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835513776  17 PVDIYSHQ------VRIVLAEKGVSFEIEHV---EKDNPPQDLIDLNPNQSVPTLVDRE---LTLWESRIIMEYLDERFP 84
Cdd:cd03048     1 MITLYTHGtpngfkVSIMLEELGLPYEIHPVdisKGEQKKPEFLKINPNGRIPAIVDHNgtpLTVFESGAILLYLAEKYD 80

glutathione S-transferase DHAR1

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835513776  21 YSHQVRIVLAEKGVSFEIEHVEKDNPPQDLIDLNPNQSVPTLVDRELTLWESRIIMEYLDERFPHPPLMPVYPVARGESR 100
Cdd:PLN02378   22 FSQRALLTLEEKSLTYKIHLINLSDKPQWFLDISPQGKVPVLKIDDKWVTDSDVIVGILEEKYPDPPLKTPAEFASVGSN 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835513776 101 LymhriekdwYSLMEVIMSSSGAQaDNARRQLREELMQIAPVFGQK--PYFLSDEFSLVDCYLAPLLWRLPILGIELSGA 178
Cdd:PLN02378  102 I---------FGTFGTFLKSKDSN-DGSEHALLVELEALENHLKSHdgPFIAGERVSAVDLSLAPKLYHLQVALGHFKSW 171

                         170       180
                  ....*....|....*....|....*...
gi 1835513776 179 GSKE----LKGYMTRVFERDSFLASLTE 202
Cdd:PLN02378  172 SVPEsfphVHNYMKTLFSLDSFEKTKTE 199

GST_N family, Class Delta and Epsilon 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. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The class Delta and Epsilon subfamily is made up primarily of insect GSTs, which play major roles in insecticide resistance by facilitating reductive dehydrochlorination of insecticides or conjugating them with GSH to produce water-soluble metabolites that are easily excreted. They are also implicated in protection against cellular damage by oxidative stress.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1835513776  11 MTLFSGPVDIYSHQVRIVLAEKGVSFEIEHV---EKDNPPQDLIDLNPNQSVPTLVDRELTLWESRIIMEYL 79
Cdd:cd03045     1 IDLYYLPGSPPCRAVLLTAKALGLELNLKEVnlmKGEHLKPEFLKLNPQHTVPTLVDNGFVLWESHAILIYL 72

GST_N family, Class Tau 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The plant-specific class Tau GST subfamily has undergone extensive gene duplication. The Arabidopsis and Oryza genomes contain 28 and 40 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Phi GSTs, showing class specificity in substrate preference. Tau enzymes are highly efficient in detoxifying diphenylether and aryloxyphenoxypropionate herbicides. In addition, Tau GSTs play important roles in intracellular signalling, biosynthesis of anthocyanin, responses to soil stresses and responses to auxin and cytokinin hormones.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1835513776  21 YSHQVRIVLAEKGVSFeiEHVEKD--NPPQDLIDLNP-NQSVPTLVDRELTLWESRIIMEYLDERF 83
Cdd:cd03058    11 FVLRVRIALALKGVPY--EYVEEDlgNKSELLLASNPvHKKIPVLLHNGKPICESLIIVEYIDEAW 74

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835513776 110 WYSLMEVIMSSSGAQADNARRQLREELMQIAPVFGQKPYFLSDEFSLVDCYLAPLLWRLPILG-IELSGAGSKELKGYMT 188
Cdd:cd00299    19 LLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEALGpYYDLLDEYPRLKAWYD 98

                  ..
gi 1835513776 189 RV 190
Cdd:cd00299    99 RL 100

GST_N family, Class Omega 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. They contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism. Polymorphisms of the class Omega GST genes may be associated with the development of some types of cancer and the age-at-onset of both Alzheimer's and Parkinson's diseases.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1835513776  21 YSHQVRIVLAEKGVSFEIEHVEKDNPPQDLIDLNPNQSVPTL-VDRELTLWESRIIMEYLD 80
Cdd:cd03055    29 YAQRARLVLAAKNIPHEVININLKDKPDWFLEKNPQGKVPALeIDEGKVVYESLIICEYLD 89

GST_N family, unknown subfamily 2; composed of uncharacterized bacterial proteins with similarity to GSTs. 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. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The sequence from Burkholderia cepacia was identified as part of a gene cluster involved in the degradation of 2,4,5-trichlorophenoxyacetic acid. Some GSTs (e.g. Class Zeta and Delta) are known to catalyze dechlorination reactions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1835513776  22 SHQVRIVL---AEKGVSFEIEHVEKD---NPPQDLIDLNPNQSVPTLVDRELTLWESRIIMEYL 79
Cdd:cd03047     9 SINVQKVLwllDELGLPYERIDAGGQfggLDTPEFLAMNPNGRVPVLEDGDFVLWESNAILRYL 72

Glutathione S-transferase, C-terminal domain; This domain is closely related to pfam00043.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1835513776 124 QADNARRQLREELMQIAPVFGQKPYFLSDEFSLVDCYLAPLLWRL 168
Cdd:pfam13410   1 ALERAREQLRAALDALEARLADGPGLLGDRPTLADIALAPVLARL 45

GST_N family, unknown subfamily 1; composed of uncharacterized proteins, predominantly from bacteria, with similarity to GSTs. 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. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1835513776  27 IVLAEKGVSFEIEHVEKDNP--PQDLIDLNPNQSVPTLVDRELTLWESRIIMEYL 79
Cdd:cd03043    18 LLLKAAGIPFEEILVPLYTPdtRARILEFSPTGKVPVLVDGGIVVWDSLAICEYL 72

glutathione S-transferase

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1835513776  23 HQVRIVLAEKGVSFEIEHVEKDN----PPQDLIDlNPNQSVPTLVDRELTLWESRIIMEYLDERF 83
Cdd:PLN02473   15 QRVLLCFLEKGIEFEVIHVDLDKleqkKPEHLLR-QPFGQVPAIEDGDLKLFESRAIARYYATKY 78

GST_N family, Class Theta subfamily; composed of eukaryotic class Theta GSTs and bacterial dichloromethane (DCM) dehalogenase. 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Mammalian class Theta GSTs show poor GSH conjugating activity towards the standard substrates, CDNB and ethacrynic acid, differentiating them from other mammalian GSTs. GSTT1-1 shows similar cataytic activity as bacterial DCM dehalogenase, catalyzing the GSH-dependent hydrolytic dehalogenation of dihalomethanes. This is an essential process in methylotrophic bacteria to enable them to use chloromethane and DCM as sole carbon and energy sources. The presence of polymorphisms in human GSTT1-1 and its relationship to the onset of diseases including cancer is subject of many studies. Human GSTT2-2 exhibits a highly specific sulfatase activity, catalyzing the cleavage of sulfate ions from aralkyl sufate esters, but not from aryl or alkyl sulfate esters.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1835513776  13 LFSGPvdiySHQVRIVLAEKGVSFEIEHV---EKDNPPQDLIDLNPNQSVPTLVDRELTLWESRIIMEYLDERF 83
Cdd:cd03050     7 LMSQP----SRAVYIFLKLNKIPFEECPIdlrKGEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

Thioredoxin (TRX) superfamily; a large, diverse group of proteins containing a TRX-fold. Many members contain a classic TRX domain with a redox active CXXC motif. They function as protein disulfide oxidoreductases (PDOs), altering the redox state of target proteins via the reversible oxidation of their active site dithiol. The PDO members of this superfamily include TRX, protein disulfide isomerase (PDI), tlpA-like, glutaredoxin, NrdH redoxin, and the bacterial Dsb (DsbA, DsbC, DsbG, DsbE, DsbDgamma) protein families. Members of the superfamily that do not function as PDOs but contain a TRX-fold domain include phosducins, peroxiredoxins and glutathione (GSH) peroxidases, SCO proteins, GSH transferases (GST, N-terminal domain), arsenic reductases, TRX-like ferredoxins and calsequestrin, among others.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1835513776  11 MTLFSGPVDIYSHQVRIVLAE-----KGVSFEIEHVEKDNPPQDLIDLNPNQSVPTLVD 64
Cdd:cd01659     1 LVLFYAPWCPFCQALRPVLAElallnKGVKFEAVDVDEDPALEKELKRYGVGGVPTLVV 59

C-terminal, alpha helical domain of Ganglioside-induced differentiation-associated protein 1-like proteins; Glutathione S-transferase (GST) C-terminal domain family, Ganglioside-induced differentiation-associated protein 1 (GDAP1)-like subfamily; GDAP1 was originally identified as a highly expressed gene at the differentiated stage of GD3 synthase-transfected cells. More recently, mutations in GDAP1 have been reported to cause both axonal and demyelinating autosomal-recessive Charcot-Marie-Tooth (CMT) type 4A neuropathy. CMT is characterized by slow and progressive weakness and atrophy of muscles. Sequence analysis of GDAP1 shows similarities and differences with GSTs; it appears to contain both N-terminal thioredoxin-fold and C-terminal alpha helical domains of GSTs, however, it also contains additional C-terminal transmembrane domains unlike GSTs. GDAP1 is mainly expressed in neuronal cells and is localized in the mitochondria through its transmembrane domains. It does not exhibit GST activity using standard substrates.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1835513776 131 QLREELMQIA---PVFGQKPYFLSDEFSLVDCYLAPLLWRLPILGIELSGAGS---KELKGYMTRVFERDSF 196
Cdd:cd03204    40 QVEKELGERKretDESGQQQWLCGESFTAADISLSVLLHRLKFLGLSRRFWGNgkrPNIESYFERVRQRESF 111