C-terminal, alpha helical domain of an unknown subfamily 2 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 953949648  86 RQRARASQWMDWQLSVQGPAITPVFWGLVRTPPEKRDPVAIDAAKKKITAAMNILNDALGKTEFVAGSDFSYGDIPVGVQ 165
Cdd:cd03180    1 AQRALADRWMDWQTSTLNPAFRYAFWGLVRTPPEQRDPAAIAASLAACNKLMAILDAQLARQAYLAGDRFTLADIALGCS 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 953949648 166 AYRYYRLLDDRPAQPNLDRWYAAISSRPAF 195
Cdd:cd03180   81 VYRWLELPIERPALPHLERWYARLSQRPAF 110

Glutathione S-transferase, N-terminal domain; This family is closely related to pfam02798.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 953949648    9 TSSNVQMAMWAVGELGLPHQRIDI-GGPFGTTPEYQKMNPNLVVPTLEEDDGFILWESKSIIRYLAEK 75
Cdd:pfam13409   1 FSPFSHRVRLALEEKGLPYEIELVdLDPKDKPPELLALNPLGTVPVLVLPDGTVLTDSLVILEYLEEL 68

C-terminal, alpha helical domain of an unknown subfamily 2 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 953949648  86 RQRARASQWMDWQLSVQGPAITPVFWGLVRTPPEKRDPVAIDAAKKKITAAMNILNDALGKTEFVAGSDFSYGDIPVGVQ 165
Cdd:cd03180    1 AQRALADRWMDWQTSTLNPAFRYAFWGLVRTPPEQRDPAAIAASLAACNKLMAILDAQLARQAYLAGDRFTLADIALGCS 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 953949648 166 AYRYYRLLDDRPAQPNLDRWYAAISSRPAF 195
Cdd:cd03180   81 VYRWLELPIERPALPHLERWYARLSQRPAF 110

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 953949648  40 PEYQKMNPNLVVPTLEEDDgFILWESKSIIRYLAEKHNGA---ILPKDVRQRARASQWMDWQLSVQGPAITP-----VFW 111
Cdd:PLN02395  42 PEYLALQPFGVVPVIVDGD-YKIFESRAIMRYYAEKYRSQgpdLLGKTIEERGQVEQWLDVEATSYHPPLLNltlhiLFA 120

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 953949648 112 GLVRTPPEKRdpvAIDAAKKKITAAMNILNDALGKTEFVAGSDFSYGDI-----------PVGvQAYryyrLLDDRpaqP 180
Cdd:PLN02395 121 SKMGFPADEK---VIKESEEKLAKVLDVYEARLSKSKYLAGDFVSLADLahlpfteylvgPIG-KAY----LIKDR---K 189

                        170       180
                 ....*....|....*....|....
gi 953949648 181 NLDRWYAAISSRPAFKEQVAAVPF 204
Cdd:PLN02395 190 HVSAWWDDISSRPAWKEVLAKYSL 213

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 953949648   2 LKIWGRNTSSNVQMAMWAVGELGLPHQRIDIGGPFGTTPEYQKMNPNLVVPTLEEdDGFILWESKSIIRYLA 73
Cdd:cd00570    1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQEEFLALNPLGKVPVLED-GGLVLTESLAILEYLA 71

C-terminal, alpha helical domain of an unknown subfamily 6 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 6; composed of uncharacterized bacterial proteins with similarity to GSTs, including Pseudomonas fluorescens GST with a known three-dimensional structure. 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 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. Though the three-dimensional structure of Pseudomonas fluorescens GST has been determined, there is no information on its functional characterization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 953949648 117 PPEKRDPVAIDAAKKKITAAMNILNDALGKTEfvaGSDFSYGDIPVGVqAYRYYRL----LDDRPAQPNLDRWYAAISSR 192
Cdd:cd03205   26 PEEKQHQPWIERQWGKIERALDALEAELGDLP---GGRLTLGDIAVAC-ALGYLDFrfpeLDWRAGHPALAAWFARFEAR 101

                 ....*
gi 953949648 193 PAFKE 197
Cdd:cd03205  102 PSFQA 106

C-terminal, alpha helical domain of Class Phi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Phi subfamily; composed of plant-specific class Phi GSTs and related fungal and bacterial proteins. 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 Phi GST subfamily has experience extensive gene duplication. The Arabidopsis and Oryza genomes contain 13 and 16 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Tau GSTs, showing class specificity in substrate preference. Phi enzymes are highly reactive toward chloroacetanilide and thiocarbamate herbicides. Some Phi GSTs have other functions including transport of flavonoid pigments to the vacuole, shoot regeneration and GSH peroxidase activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 953949648  87 QRARASQWMDWQLSVQGPAITPVFWGLVRTPP--EKRDPVAIDAAKKKITAAMNILNDALGKTEFVAGSDFSYGD---IP 161
Cdd:cd03187    2 ERALVEQWLEVEAHQFDPPASKLVFELVFKPMlgLKTDEAVVEENEAKLKKVLDVYEARLSKSKYLAGDSFTLADlshLP 81

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 953949648 162 VG--VQAYRYYRLLDDRPaqpNLDRWYAAISSRPAFK 196
Cdd:cd03187   82 NLhyLMATPSKKLFDSRP---HVKAWWEDISARPAWK 115

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 953949648  22 ELGLPHQRIDIGGPFGT--TPEYQKMNPNLVVPTLEEDD--GFILWESKSIIRYLAEKHN 77
Cdd:cd03048   21 ELGLPYEIHPVDISKGEqkKPEFLKINPNGRIPAIVDHNgtPLTVFESGAILLYLAEKYD 80

Glutathione S-transferase C-terminal-like, alpha helical domain of the Gamma subunit of Elongation Factor 1B and similar proteins; Glutathione S-transferase (GST) C-terminal domain family, Gamma subunit of Elongation Factor 1B (EF1Bgamma) subfamily; EF1Bgamma is part of the eukaryotic translation elongation factor-1 (EF1) complex which plays a central role in the elongation cycle during protein biosynthesis. EF1 consists of two functionally distinct units, EF1A and EF1B. EF1A catalyzes the GTP-dependent binding of aminoacyl-tRNA to the ribosomal A site concomitant with the hydrolysis of GTP. The resulting inactive EF1A:GDP complex is recycled to the active GTP form by the guanine-nucleotide exchange factor EF1B, a complex composed of at least two subunits, alpha and gamma. Metazoan EFB1 contain a third subunit, beta. The EF1B gamma subunit contains a GST fold consisting of an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The GST-like domain of EF1Bgamma is believed to mediate the dimerization of the EF1 complex, which in yeast is a dimer of the heterotrimer EF1A:EF1Balpha:EF1Bgamma. In addition to its role in protein biosynthesis, EF1Bgamma may also display other functions. The recombinant rice protein has been shown to possess GSH conjugating activity. The yeast EF1Bgamma binds to membranes in a calcium dependent manner and is also part of a complex that binds to the msrA (methionine sulfoxide reductase) promoter suggesting a function in the regulation of its gene expression. Also included in this subfamily is the GST_C-like domain at the N-terminus of human valyl-tRNA synthetase (ValRS) and its homologs. Metazoan ValRS forms a stable complex with Elongation Factor-1H (EF-1H), and together, they catalyze consecutive steps in protein biosynthesis, tRNA aminoacylation and its transfer to EF.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 953949648  87 QRARASQWMDW-QLSVQGPAITPVFWGLVRTPpekRDPVAIDAAKKKITAAMNILNDALGKTEFVAGSDFSYGDIPVGVQ 165
Cdd:cd03181    1 EAAQVLQWISFaNSELLPAAATWVLPLLGIAP---YNKKAVDKAKEDLKRALGVLEEHLLTRTYLVGERITLADIFVASA 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 953949648 166 AYRYYRLLDD---RPAQPNLDRWYAAISSRPAFKEQVAAVPFV 205
Cdd:cd03181   78 LLRGFETVLDpefRKKYPNVTRWFNTVVNQPKFKAVFGEVKLC 120

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 953949648    6 GRNTSSNVQMAMWAVGELGLPHQRIDIGgPFGTTPEYQKMNPNLVVPTLEeDDGFILWESKSIIRYLAEKHNG 78
Cdd:pfam13417   3 GFPGSPYARRVRIALNEKGLPYEFVPIP-PGDHPPELLAKNPLGKVPVLE-DDGGILCESLAIIDYLEELYPG 73

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 953949648  88 RARASQWMDWQLSVQGPAITPVFWGLvRTPPEKrDPVAIDAAKKKITAAMNILNDALGKTEFVAGSDFSYGDI---PVGV 164
Cdd:cd03178    2 RAEVLQWLFFQMSGLGPMFGQAGHFL-YFAPEK-IPYAIERYTDEVKRLYGVLDKRLSDRPYLAGEEYSIADIalyPWTH 79

                         90       100       110
                 ....*....|....*....|....*....|...
gi 953949648 165 QAYRYYrlLDDRPAQPNLDRWYAAISSRPAFKE 197
Cdd:cd03178   80 YADLGG--FADLSEYPNVKRWLERIAARPAVQK 110

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
                 ....*....|....*....|....*....|....*.
gi 953949648  39 TPEYQKMNPNLVVPTLEeDDGFILWESKSIIRYLAE 74
Cdd:cd03045   40 KPEFLKLNPQHTVPTLV-DNGFVLWESHAILIYLVE 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 953949648  93 QWMDWQLSVQGPAITPVFWglVRTPPEKRDPVAIDAAKKKITAAMNILNDALGKTEFVAGSDFSYGDIPVGVQAYRYYRL 172
Cdd:cd00299    3 ALEDWADATLAPPLVRLLY--LEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEAL 80

                         90       100
                 ....*....|....*....|
gi 953949648 173 L---DDRPAQPNLDRWYAAI 189
Cdd:cd00299   81 GpyyDLLDEYPRLKAWYDRL 100

C-terminal, alpha helical domain of Escherichia coli YfcG Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YfcG-like subfamily; composed of the Escherichia coli YfcG and related proteins. 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 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. YfcG is one of nine GST homologs in Escherichia coli. It is expressed predominantly during the late stationary phase where the predominant form of GSH is glutathionylspermidine (GspSH), suggesting that YfcG might interact with GspSH. It has very low or no GSH transferase or peroxidase activity, but displays a unique disulfide bond reductase activity that is comparable to thioredoxins (TRXs) and glutaredoxins (GRXs). However, unlike TRXs and GRXs, YfcG does not contain a redox active cysteine residue and may use a bound thiol disulfide couple such as 2GSH/GSSG for activity. The crystal structure of YcfG reveals a bound GSSG molecule in its active site. The actual physiological substrates for YfcG are yet to be identified.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 953949648  87 QRARASQWMDWQLSVQGPAI--TPVFwglVRTPPEKRdPVAIDAAKKKITAAMNILNDALGKTEFVAGSDFSYGDIPVGV 164
Cdd:cd10291    1 ERYAVLQWLMWQMGGLGPMQgqAHHF---KRYAPEKI-PYAIKRYTNETKRLYGVLDRRLAKSKYLAGDEYSIADIAIWP 76

                         90       100       110
                 ....*....|....*....|....*....|...
gi 953949648 165 QAYRYYRLLDDRPAQPNLDRWYAAISSRPAFKE 197
Cdd:cd10291   77 WVARHEWQGIDLADFPNLKRWFERLAARPAVQK 109

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 953949648    2 LKIWGRNTSSNVQMAMWAVGELGLPHQ--RIDIGGPFGTTPEYQKMNPNLVVPTLEeDDGFILWESKSIIRYLAE 74
Cdd:pfam02798   3 LTLYGIRGSPRAHRIRWLLAEKGVEYEivPLDFGAGPEKSPELLKLNPLGKVPALE-DGGKKLTESRAILEYIAR 76

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 953949648  15 MAMW-AVGELGLPHQ--RIDIGGPFGTTPEYQKMNPNLVVPTLEEDDgFILWESKSIIRYLAEK----HNGAILPKDVRQ 87
Cdd:PRK15113  20 MSAFvALQEKGLPFElkTVDLDAGEHLQPTYQGYSLTRRVPTLQHDD-FELSESSAIAEYLEERfappAWERIYPADLQA 98

                         90
                 ....*....|
gi 953949648  88 RARASQWMDW 97
Cdd:PRK15113  99 RARARQIQAW 108

C-terminal, alpha helical domain of GTT2-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the Saccharomyces cerevisiae GST protein, GTT2. 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 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. GTT2, a homodimer, exhibits GST activity with standard substrates. Strains with deleted GTT2 genes are viable but exhibit increased sensitivity to heat shock.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 953949648 130 KKKITAAMNILNDALGKTEFVAGSDFSYGDIpVGVQAYRYYRLLDDRP--AQPNLDRWYAAISSRPAF 195
Cdd:cd03182   50 KKRVIDFLPVLDKRLAESPYVAGDRFSIADI-TAFVALDFAKNLKLPVpeELTALRRWYERMAARPSA 116

C-terminal, alpha helical domain of Class Theta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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 the 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 the aryl or alkyl sulfate esters.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 953949648  88 RARASQWMDWQ-LSVQGPAiTPVFWGLVRTP---PEKRDPVAIDAAKKKITAAMNILNDA-LGKTEFVAGSDFSYGDI-- 160
Cdd:cd03183    2 RARVDEYLAWQhTNLRLGC-AAYFWQKVLLPlfgGTPVSPEKVKKAEENLEESLDLLENKfLKDKPFLAGDEISIADLsa 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 953949648 161 ------PVGVQayryYRLLDDRpaqPNLDRWYAAISSR--PAFKE 197
Cdd:cd03183   81 iceimqPEAAG----YDVFEGR---PKLAAWRKRVKEAgnPLFDE 118

GST_N family, Class Zeta 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 Zeta GSTs, also known as maleylacetoacetate (MAA) isomerases, catalyze the isomerization of MAA to fumarylacetoacetate, the penultimate step in tyrosine/phenylalanine catabolism, using GSH as a cofactor. They show little GSH-conjugating activity towards traditional GST substrates but display modest GSH peroxidase activity. They are also implicated in the detoxification of the carcinogen dichloroacetic acid by catalyzing its dechlorination to glyoxylic acid.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 953949648  39 TPEYQKMNPNLVVPTLeEDDGFILWESKSIIRYL 72
Cdd:cd03042   40 SPAYRALNPQGLVPTL-VIDGLVLTQSLAIIEYL 72

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 953949648  104 PAITPVFWGLVRTPPEKRDPVAiDAAKKKITAAMNILNDALGKTEFVAGSDFSYGDIpVGVQAYRYYRLLD---DRPAQP 180
Cdd:pfam00043   3 DLRMQIALLPYVPPEEKKEPEV-DEALEKVARVLSALEEVLKGQTYLVGDKLTLADI-ALAPALLWLYELDpacLREKFP 80

                          90
                  ....*....|...
gi 953949648  181 NLDRWYAAISSRP 193
Cdd:pfam00043  81 NLKAWFERVAARP 93

glutaredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 953949648  50 VVPTLEEDDGFILWESKSIIRYLAEKHNGAILPKDVRQRARasqwmDWQLSVQGPA---ITPVFWGLVRtpPEKRDPVAI 126
Cdd:PRK10387  47 QVPILQKDDGSYMPESLDIVHYIDELDGKPLLTGKRSPAIE-----EWLRKVFGYLnklLYPRFAKADL--PEFATPSAR 119

                         90       100
                 ....*....|....*....|.
gi 953949648 127 DAAKKKITAAMNILNDALGKT 147
Cdd:PRK10387 120 QYFIDKKEASIGDFDALLAHT 140

C-terminal, alpha helical domain of Escherichia coli Yghu Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YghU-like subfamily; composed of the Escherichia coli YghU and related proteins. 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 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. YghU is one of nine GST homologs in the genome of Escherichia coli. It is similar to Escherichia coli YfcG in that it has poor GSH transferase activity towards typical substrates. It shows modest reductase activity towards some organic hydroperoxides. Like YfcG, YghU also shows good disulfide bond oxidoreductase activity comparable to the activities of glutaredoxins and thioredoxins. YghU does not contain a redox active cysteine residue, and may use a bound thiol disulfide couple such as 2GSH/GSSG for activity. The crystal structure of YghU reveals two GSH molecules bound in its active site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 953949648  88 RARASQWMDWQLSvQGPAITPVFWGLVRTPPEKRDpVAIDAAKKKITAAMNILNDALGKTEFVAGSDFSYGDIPVgvqaY 167
Cdd:cd10292    2 RTETLNWLFWQMG-SAPYLGGGFGHFYSYAPVKIE-YAIDRFTMEAKRQLDVLDRQLATHKYLAGDEYTIADMAI----W 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 953949648 168 RYY------RLLD-----DRPAQPNLDRWYAAISSRPAFK 196
Cdd:cd10292   76 PWYgglalgSLYDaaeflDVDEYKHVQRWAKDIAARPAVK 115