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 357132163  93 KEAAMVDVWTEVDAHTYNPALSPIVYECLINPMMrGIPTNQKVVDESLEKLKKVLEVYEAHLSKHKYLAGDFISFADLNH 172
Cdd:cd03187    1 KERALVEQWLEVEAHQFDPPASKLVFELVFKPML-GLKTDEAVVEENEAKLKKVLDVYEARLSKSKYLAGDSFTLADLSH 79

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 357132163 173 FPYTFYFMGTPHAALFDSYPHVKAWWERIMARPSVQKL 210
Cdd:cd03187   80 LPNLHYLMATPSKKLFDSRPHVKAWWEDISARPAWKKV 117

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 357132163  109 YNPALSPIVYECLINPmmrgIPTNQKVVDESLEKLKKVLEVYEAHLSKHKYLAGDFISFADLNHFPYTFYFMGTPHAALF 188
Cdd:pfam00043   1 LMDLRMQIALLPYVPP----EEKKEPEVDEALEKVARVLSALEEVLKGQTYLVGDKLTLADIALAPALLWLYELDPACLR 76

                          90
                  ....*....|....*..
gi 357132163  189 DSYPHVKAWWERIMARP 205
Cdd:pfam00043  77 EKFPNLKAWFERVAARP 93

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 357132163  93 KEAAMVDVWTEVDAHTYNPALSPIVYECLINPMMrGIPTNQKVVDESLEKLKKVLEVYEAHLSKHKYLAGDFISFADLNH 172
Cdd:cd03187    1 KERALVEQWLEVEAHQFDPPASKLVFELVFKPML-GLKTDEAVVEENEAKLKKVLDVYEARLSKSKYLAGDSFTLADLSH 79

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 357132163 173 FPYTFYFMGTPHAALFDSYPHVKAWWERIMARPSVQKL 210
Cdd:cd03187   80 LPNLHYLMATPSKKLFDSRPHVKAWWEDISARPAWKKV 117

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357132163   5 KVFGPAMSTNVARVLVCLEEVGAEYEVVNIDFQAQEHKSPEHLVRNPFGQIPAFQDGDLLLFESRAISKYVLRKYktDKV 84
Cdd:COG0625    3 KLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERY--PEP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357132163  85 DLLREGnLKEAAMVDVWTEVDAHTYNPALSPIVYeclinpMMRGIPtNQKVVDESLEKLKKVLEVYEAHLSKHKYLAGDF 164
Cdd:COG0625   81 PLLPAD-PAARARVRQWLAWADGDLHPALRNLLE------RLAPEK-DPAAIARARAELARLLAVLEARLAGGPYLAGDR 152

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 357132163 165 ISFADLNHFPYTFYFMGtpHAALFDSYPHVKAWWERIMARPSVQK 209
Cdd:COG0625  153 FSIADIALAPVLRRLDR--LGLDLADYPNLAAWLARLAARPAFQR 195

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 357132163  109 YNPALSPIVYECLINPmmrgIPTNQKVVDESLEKLKKVLEVYEAHLSKHKYLAGDFISFADLNHFPYTFYFMGTPHAALF 188
Cdd:pfam00043   1 LMDLRMQIALLPYVPP----EEKKEPEVDEALEKVARVLSALEEVLKGQTYLVGDKLTLADIALAPALLWLYELDPACLR 76

                          90
                  ....*....|....*..
gi 357132163  189 DSYPHVKAWWERIMARP 205
Cdd:pfam00043  77 EKFPNLKAWFERVAARP 93

GST_N family, Saccharomyces cerevisiae GTT1-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. cerevisiae GST protein, GTT1, and the Schizosaccharomyces pombe GST-III. 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. GTT1, a homodimer, exhibits GST activity with standard substrates and associates with the endoplasmic reticulum. Its expression is induced after diauxic shift and remains high throughout the stationary phase. S. pombe GST-III is implicated in the detoxification of various metals.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 357132163  17 RVLVCLEEVGAEYEVVNIDFQAQEHKSPEHLVRNPFGQIPAFQDGDLLLFESRAISKYVLRKY 79
Cdd:cd03046   13 RILWLLEELGLPYELVLYDRGPGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEKY 75

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 357132163   4 VKVFGPAMSTNVARVLVCLEEVGAEYEVVNIDFQAQEHKspEHLVRNPFGQIPAFQDGDLLLFESRAISKYV 75
Cdd:cd00570    1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQE--EFLALNPLGKVPVLEDGGLVLTESLAILEYL 70

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 357132163  14 NVARVLVCLEEVGAEYEVVNIDFQAQEHKSPEHLVRNPFGQIPAFQD---GDLLLFESRAISKYVLRKY 79
Cdd:cd03048   11 NGFKVSIMLEELGLPYEIHPVDISKGEQKKPEFLKINPNGRIPAIVDhngTPLTVFESGAILLYLAEKY 79

GST_N family, unknown subfamily 4; 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 357132163   5 KVFGPAMSTNVARVLVCLEEVGAEYEVVNIDFQAQEHKSPEHLVRNPFGQIPAFQDGDLLLFESRAISKYV 75
Cdd:cd03056    2 KLYGFPLSGNCYKVRLLLALLGIPYEWVEVDILKGETRTPEFLALNPNGEVPVLELDGRVLAESNAILVYL 72

C-terminal, alpha helical domain of GTT1-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae GTT1-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. cerevisiae GST protein, GTT1, and the Schizosaccharomyces pombe GST-III. 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. GTT1, a homodimer, exhibits GST activity with standard substrates and associates with the endoplasmic reticulum. Its expression is induced after diauxic shift and remains high throughout the stationary phase. S. pombe GST-III is implicated in the detoxification of various metals.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357132163 124 PMMRGIPTNQKVVDESLEK-----LKKVLEVYEAHLSKHKYLAGDFISFAD-LNHFPYTFYFMGTPhaaLFDSYPHVKAW 197
Cdd:cd03189   39 PPPFFRPISRKIADKPLQAfinpeLKRHLDFLEDHLAKHPYFAGDELTAADiMMSFPLEAALARGP---LLEQYPNIAAY 115

                 ....*...
gi 357132163 198 WERIMARP 205
Cdd:cd03189  116 LERIEARP 123

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 357132163   4 VKVFGPAMSTNVARVLVCLEEVGAEYEVVNIDFQAQEHKSPEHLVRNPFGQIPAFQDGDLLLFESRAISKYVLRKY 79
Cdd:cd03050    1 LKLYYDLMSQPSRAVYIFLKLNKIPFEECPIDLRKGEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 357132163 144 KKVLEVYEAHLSKHKYLAGDFISFADLNHFPYTFYFMGtpHAALFDSYPHVKAWWERIMARPSVQK 209
Cdd:cd10291   46 KRLYGVLDRRLAKSKYLAGDEYSIADIAIWPWVARHEW--QGIDLADFPNLKRWFERLAARPAVQK 109

GST_N family, Gamma subunit of Elongation Factor 1B (EFB1gamma) 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 TRX-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 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 357132163   5 KVFGPAMSTNVARVLVCLEEVGAEYEVVNiDFQAQEHKSPEHLVRNPFGQIPAFQDGD-LLLFESRAISKYVLRK 78
Cdd:cd03044    2 TLYTYPGNPRSLKILAAAKYNGLDVEIVD-FQPGKENKTPEFLKKFPLGKVPAFEGADgFCLFESNAIAYYVANL 75

GST_N family, Class Beta 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. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit limited GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they also bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 357132163  22 LEEVGAEYEVVNIDFQAQEHKSPEHLVRNPFGQIPAFQDGD-LLLFESRAISKYVLRKY 79
Cdd:cd03057   18 LEELGLPFELVRVDLRTKTQKGADYLAINPKGQVPALVLDDgEVLTESAAILQYLADLH 76

C-terminal, alpha helical domain of an unknown subfamily 7 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 7; composed of uncharacterized 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 357132163 136 VDESLEKLKKVLEVYEAHLSKHKYLAGDFISFADLNHFPYtfyfmgTPHA-----ALfDSYPHVKAWWERIMARP 205
Cdd:cd03206   31 PERARAISHRLLRLLDQHLAGRDWLAGDRPTIADVACYPY------IALApeggvSL-EPYPAIRAWLARVEALP 98

GST_N family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 357132163   5 KVFGPAMSTNVARVLVCLEEVGAEYEVVNIDFQAQEHKSPEHLVRNPFGQIPAFQ-DGDLLLFESRAISKYV 75
Cdd:cd03051    2 KLYDSPTAPNPRRVRIFLAEKGIDVPLVTVDLAAGEQRSPEFLAKNPAGTVPVLElDDGTVITESVAICRYL 73

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 357132163 144 KKVLEVYEAHLSKHKYLAGDFISFADLNHFP-YTFYFMGTPH-AALF---DSYPHVKAWWERIMARPSVQK 209
Cdd:cd10292   46 KRQLDVLDRQLATHKYLAGDEYTIADMAIWPwYGGLALGSLYdAAEFldvDEYKHVQRWAKDIAARPAVKR 116

C-terminal, alpha helical domain of Class Beta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Beta 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. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they are involved in the protection against oxidative stress and are able to bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs, contributing to antibiotic resistance. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH. One member of this subfamily is a GST from Burkholderia xenovorans LB400 that is encoded by the bphK gene and is part of the biphenyl catabolic pathway.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 357132163 140 LEKLKKVLEVYEAHLSKHKYLAGDFISFADlnhfPYTFYFMG-TPHAALF-DSYPHVKAWWERIMARPSVQK 209
Cdd:cd03188   44 RERLERRLAYLDAQLAGGPYLLGDQFSVAD----AYLFVVLRwARAVGLDlSDWPHLAAYLARVAARPAVQA 111

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 357132163   12 STNVARVLVCLEEVGAEYEVVNIDfqaQEHKSPEHLVRNPFGQIPAFQDGDLLLFESRAISKYVLRKY 79
Cdd:pfam13417   7 SPYARRVRIALNEKGLPYEFVPIP---PGDHPPELLAKNPLGKVPVLEDDGGILCESLAIIDYLEELY 71

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357132163 122 INPMMRG--IPTNQKVVDESLEKLKKVLEVYEAHLSKHKYLAGDFISFADLNHFpYTFYFMGTPHAALFDSYPHVKAWWE 199
Cdd:cd03182   30 ATPGLKPdrEVQVPEWGERNKKRVIDFLPVLDKRLAESPYVAGDRFSIADITAF-VALDFAKNLKLPVPEELTALRRWYE 108

                 ....*...
gi 357132163 200 RIMARPSV 207
Cdd:cd03182  109 RMAARPSA 116

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 357132163 138 ESLEKLKKVLEVYEahlsKHKYLAGDFISFADLNHFPYTF-YFMGTPHAalFDSYPHVKAWWERIMARPSVQK 209
Cdd:cd03210   42 EQLKPFEKLLAKNN----GKGFIVGDKISFADYNLFDLLDiHLVLAPGC--LDAFPLLKAFVERLSARPKLKA 108

glutathione transferase;

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357132163   7 FGP-AMStnvarVLVCLEEVGAEYEVVNIDFQAQEHKSPEHLVRNPFGQIPAFQDGDLLLFESRAISKYV 75
Cdd:PRK15113  15 FSPyVMS-----AFVALQEKGLPFELKTVDLDAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYL 79

C-terminal, alpha helical domain of Class Sigma-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Sigma_like; composed of GSTs belonging to class Sigma and similar proteins, including GSTs from class Mu, Pi, and Alpha. 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. Vertebrate class Sigma GSTs are characterized as GSH-dependent hematopoietic prostaglandin (PG) D synthases and are responsible for the production of PGD2 by catalyzing the isomerization of PGH2. The functions of PGD2 include the maintenance of body temperature, inhibition of platelet aggregation, bronchoconstriction, vasodilation, and mediation of allergy and inflammation. Other class Sigma-like members include the class II insect GSTs, S-crystallins from cephalopods, nematode-specific GSTs, and 28-kDa GSTs from parasitic flatworms. Drosophila GST2 is associated with indirect flight muscle and exhibits preference for catalyzing GSH conjugation to lipid peroxidation products, indicating an anti-oxidant role. S-crystallin constitutes the major lens protein in cephalopod eyes and is responsible for lens transparency and proper refractive index. The 28-kDa GST from Schistosoma is a multifunctional enzyme, exhibiting GSH transferase, GSH peroxidase, and PGD2 synthase activities, and may play an important role in host-parasite interactions. Members also include novel GSTs from the fungus Cunninghamella elegans, designated as class Gamma, and from the protozoan Blepharisma japonicum, described as a light-inducible GST.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 357132163 133 QKVVDESLEKLKKVLEVYEAHLSKHK--YLAGDFISFADL---NHFPYTFYFMGTPhaaLFDSYPHVKAWWERI 201
Cdd:cd03192   34 EKKKEFLEEALPKFLGKFEKILKKSGggYFVGDKLTWADLalfDVLDYLLYLLPKD---LLEKYPKLKALRERV 104

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357132163 111 PALSPIVYECLInPMMRGIPTNQKVVDESLEKLKKVLEVYE-AHLSKHKYLAGDFISFADLNHFPytfYFMgTPHAA--- 186
Cdd:cd03183   19 GCAAYFWQKVLL-PLFGGTPVSPEKVKKAEENLEESLDLLEnKFLKDKPFLAGDEISIADLSAIC---EIM-QPEAAgyd 93

                         90
                 ....*....|....*...
gi 357132163 187 LFDSYPHVKAWWERIMAR 204
Cdd:cd03183   94 VFEGRPKLAAWRKRVKEA 111

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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 tumours.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 357132163   3 PVKVFGPAMstnvaRVLVCLEEVGAEYEVVNIDFQAQEHKSpehlvRNPFGQIPAFQDGDLLLFESRAISKYVLRK 78
Cdd:cd03076    8 PVRGRAEAI-----RLLLADQGISWEEERVTYEEWQESLKP-----KMLFGQLPCFKDGDLTLVQSNAILRHLGRK 73

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.

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gi 357132163   4 VKVFGPAMSTNVARVLVCLEEVGAEYEVVNIDFQAqehKSPEHLVRNP-FGQIPAFQDGDLLLFESRAISKYV 75
Cdd:cd03058    1 VKLLGAWASPFVLRVRIALALKGVPYEYVEEDLGN---KSELLLASNPvHKKIPVLLHNGKPICESLIIVEYI 70

Glutathione S-transferase C-terminal-like, alpha helical domain of vertebrate Valyl-tRNA synthetase; Glutathione S-transferase (GST) C-terminal domain family, Valyl-tRNA synthetase (ValRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of human ValRS and its homologs from other vertebrates such as frog and zebrafish. Aminoacyl-tRNA synthetases (aaRSs) comprise a family of enzymes that catalyze the coupling of amino acids with their matching tRNAs. This involves the formation of an aminoacyl adenylate using ATP, followed by the transfer of the activated amino acid to the 3'-adenosine moiety of the tRNA. AaRSs may also be involved in translational and transcriptional regulation, as well as in tRNA processing. They typically form large stable complexes with other proteins. 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. The GST_C-like domain of ValRS from higher eukaryotes is likely involved in protein-protein interactions, to mediate the formation of the multi-aaRS complex that acts as a molecular hub to coordinate protein synthesis. ValRSs from prokaryotes and lower eukaryotes, such as fungi and plants, do not appear to contain this GST_C-like domain.

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                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 357132163 113 LSPIVYECLInPMMRGIPTNQKVVDESLEKLKKVLEVYEAHLSKHKYLAGDFISFADL 170
Cdd:cd10294   16 LTPAACAAAF-PLLGLSGSDKQNQQRSLAELQRVLKVLDCYLKLRTYLVGEAITLADI 72

C-terminal, alpha helical domain of an unknown subfamily 5 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 5; 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 357132163 147 LEVYEAHLSKHKYLAGDFISFADLNHFPYTFYFMGT-PHAALFDSYPHVKAWWERIMARP 205
Cdd:cd03196   50 LAELEARLSQHAYLFGDRPSLADYAIFPFVRQFAHVdRDWFDASPYPNLRRWLNRFLQSP 109