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 27363352  90 EDRGQVEQWLDVEATTYHPPLLNLTLHIMFASVMGFPSDEKLIKESEEKLAGVLDVYEAHLSKSKYLAGDFVSLADLAHL 169
Cdd:cd03187   1 KERALVEQWLEVEAHQFDPPASKLVFELVFKPMLGLKTDEAVVEENEAKLKKVLDVYEARLSKSKYLAGDSFTLADLSHL 80

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 27363352 170 PFTDYLVGPiGKAYMIKDRKHVSAWWDDISSRPAWKETV 208
Cdd:cd03187  81 PNLHYLMAT-PSKKLFDSRPHVKAWWEDISARPAWKKVL 118

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 27363352     1 MVLKVYG-PHFASPKRALVTLIEKGVAFETIPVDLMKGEHKQPAYLALQPFGTVPAVVDGDYKIFESRAVMRYVAE 75
Cdd:pfam02798   1 MVLTLYGiRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27363352    1 MVLKVYGP-HFASPKRALVTLIEKGVAFETIPVDLMKGEHKQPAYLALQPFGTVPAVVDGDYKIFESRAVMRYVAEKYRS 79
Cdd:PLN02473   1 MVVKVYGQiKAANPQRVLLCFLEKGIEFEVIHVDLDKLEQKKPEHLLRQPFGQVPAIEDGDLKLFESRAIARYYATKYAD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27363352   80 QGPDLLGKTVEDRGQVEQWLDVEATTYHPPLLNLTLHIMFASVMGFPSDEKLIKESEEKLAGVLDVYEAHLSKSKYLAGD 159
Cdd:PLN02473  81 QGTDLLGKTLEHRAIVDQWVEVENNYFYAVALPLVINLVFKPRLGEPCDVALVEELKVKFDKVLDVYENRLATNRYLGGD 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 27363352  160 FVSLADLAHLPFTDYLVGPIGKAYMIKDRKHVSAWWDDISSRPAWKE 206
Cdd:PLN02473 161 EFTLADLTHMPGMRYIMNETSLSGLVTSRENLNRWWNEISARPAWKK 207

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27363352   3 LKVYGpHFASP--KRALVTLIEKGVAFETIPVDLMKGEHKQPAYLALQPFGTVPAVVDGDYKIFESRAVMRYVAEKYrsQ 80
Cdd:COG0625   2 MKLYG-SPPSPnsRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERY--P 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27363352  81 GPDLLGKTVEDRGQVEQWLDVEATTYHPPLLNLTLHIMFAsvmgfpSDEKLIKESEEKLAGVLDVYEAHLSKSKYLAGDF 160
Cdd:COG0625  79 EPPLLPADPAARARVRQWLAWADGDLHPALRNLLERLAPE------KDPAAIARARAELARLLAVLEARLAGGPYLAGDR 152

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 27363352 161 VSLADLAHLPFTDYLVGPigkAYMIKDRKHVSAWWDDISSRPAWKETVAK 210
Cdd:COG0625 153 FSIADIALAPVLRRLDRL---GLDLADYPNLAAWLARLAARPAFQRALAA 199

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 27363352   3 LKVYGpHFAS-PKRALVT-LIEKGVAFETIPVDLMKGEHKQPAYLALQPFGTVPAVVDGDYKIFESRAVMRYVAEKY 77
Cdd:cd03050   1 LKLYY-DLMSqPSRAVYIfLKLNKIPFEECPIDLRKGEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

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 27363352     1 MVLKVYG-PHFASPKRALVTLIEKGVAFETIPVDLMKGEHKQPAYLALQPFGTVPAVVDGDYKIFESRAVMRYVAE 75
Cdd:pfam02798   1 MVLTLYGiRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

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 27363352   3 LKVYG-PHFASPKRALVTLIEKGVAFETIPVDLMKGEHKqpAYLALQPFGTVPAVVDGDYKIFESRAVMRYVA 74
Cdd:cd00570   1 LKLYYfPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQE--EFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

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 27363352   122 VMGFPSDEKLIKESEEKLAGVLDVYEAHLSKSKYLAGDFVSLADLAHLPFTDYlVGPIGKAYMIKDRKHVSAWWDDISSR 201
Cdd:pfam00043  14 VPPEEKKEPEVDEALEKVARVLSALEEVLKGQTYLVGDKLTLADIALAPALLW-LYELDPACLREKFPNLKAWFERVAAR 92

                  .
gi 27363352   202 P 202
Cdd:pfam00043  93 P 93

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 27363352   1 MVLkvYGPHFASPKRALVTLIEK-GVAFETIPVDLMKGEHKQPAYLALQPFGTVPAVVDGDYKIFESRAVMRYVAE 75
Cdd:cd03045   1 IDL--YYLPGSPPCRAVLLTAKAlGLELNLKEVNLMKGEHLKPEFLKLNPQHTVPTLVDNGFVLWESHAILIYLVE 74

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        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 27363352  23 KGVAFETIPVDLMKGEHKQPAYLALQPFGTVPAVVDGDYKIFESRAVMRY 72
Cdd:cd03042  22 KGLDYEYVPVNLLKGEQLSPAYRALNPQGLVPTLVIDGLVLTQSLAIIEY 71

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27363352    15 RALVTLIEKGVAFETIPVDlMKGEHKQPAYLALQPFGTVPAVVDGDYK-IFESRAVMRYVAEK 76
Cdd:pfam13409   7 RVRLALEEKGLPYEIELVD-LDPKDKPPELLALNPLGTVPVLVLPDGTvLTDSLVILEYLEEL 68

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27363352   3 LKVYG-PHFASPKRALVTLIEKGVAFETIPVDLMKGEHKQPAYLALQPFGTVPAVVDGDYKIFESRAVMRYVA 74
Cdd:cd03047   1 LTIWGrRSSINVQKVLWLLDELGLPYERIDAGGQFGGLDTPEFLAMNPNGRVPVLEDGDFVLWESNAILRYLA 73

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 27363352  92 RGQVEQWLDVEATTYHPPLLNLTLHImfasVMGFPS--DEKLIKESEEKLAGVLDVYEAHLSKSKYLAGDFVSLADLAHL 169
Cdd:cd03180   3 RALADRWMDWQTSTLNPAFRYAFWGL----VRTPPEqrDPAAIAASLAACNKLMAILDAQLARQAYLAGDRFTLADIALG 78

                        90       100       110
                ....*....|....*....|....*....|....*
gi 27363352 170 PFT-DYLVGPIGKAymikDRKHVSAWWDDISSRPA 203
Cdd:cd03180  79 CSVyRWLELPIERP----ALPHLERWYARLSQRPA 109

C-terminal, alpha helical domain of an unknown subfamily 8 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 8; composed of Agrobacterium tumefaciens GST and other 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. The three-dimensional structure of Agrobacterium tumefaciens GST has been determined but there is no information on its functional characterization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27363352  97 QWLDVEATTYHPPLLNLTLHIMFasvmGFPSDEKLIKESEEKLAGVLDVYEAHLSKSKYLAGDFVSLADLahlpFTDYLV 176
Cdd:cd03207   3 RWLFFAAGTVEPPLLNKALGRFF----EPPWGEPAIAAAYGDLDERLAALEAALAGRPYLVGERFSAADL----LLASVL 74

                        90       100
                ....*....|....*....|....*..
gi 27363352 177 GPIGKAYMIKDRKHVSAWWDDISSRPA 203
Cdd:cd03207  75 RWARAFGLLPEYPALRAYVARCTARPA 101

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 27363352  91 DRGQVEQWLDVEATTyHPPLLNLTLHI-MFASVMGFPSDEKLIKESEEklagVLDVYEAHLSKSKYLAGDFVSLADLAHL 169
Cdd:cd03178   1 ERAEVLQWLFFQMSG-LGPMFGQAGHFlYFAPEKIPYAIERYTDEVKR----LYGVLDKRLSDRPYLAGEEYSIADIALY 75

                        90       100       110
                ....*....|....*....|....*....|....
gi 27363352 170 PFTDYLVgpIGKAYMIKDRKHVSAWWDDISSRPA 203
Cdd:cd03178  76 PWTHYAD--LGGFADLSEYPNVKRWLERIAARPA 107

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 27363352  88 TVEDRGQVEQWLD-VEattyhppllnltLHIMFASVMGF--------PSDEKLIKE----SEEKLAGVLDVYEAHLSKSK 154
Cdd:cd03182   1 TPLEKALIEMWQRrAE------------LQGLAPVFQAFrhatpglkPDREVQVPEwgerNKKRVIDFLPVLDKRLAESP 68

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 27363352 155 YLAGDFVSLADLAHLPFTDYlvGPIGKAYMIKDRKHVSAWWDDISSRPA 203
Cdd:cd03182  69 YVAGDRFSIADITAFVALDF--AKNLKLPVPEELTALRRWYERMAARPS 115

putative S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27363352   17 LVTLIEKGVAFETIPVDLMKGEHKQPAYLALQPFGTVPAVVD--GD--YKIFESRAVMRYVAEKYRSqgpdLLGKTVEDR 92
Cdd:PRK11752  65 LLALGVKGAEYDAWLIRIGEGDQFSSGFVEINPNSKIPALLDrsGNppIRVFESGAILLYLAEKFGA----FLPKDLAAR 140

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27363352   93 GQVEQWLDVEATTyhPPLLNLTLHIMFASV---MGFPSDeKLIKESEEKLagvlDVYEAHLSKSKYLAGDFVSLADLAHL 169
Cdd:PRK11752 141 TETLNWLFWQQGS--APFLGGGFGHFYAYApekIEYAIN-RFTMEAKRQL----DVLDKQLAEHEYIAGDEYTIADIAIW 213

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 27363352  170 PFTDYLVgpIGKAY------MIKDRKHVSAWWDDISSRPAWK 205
Cdd:PRK11752 214 PWYGNLV--LGNLYdaaeflDVGSYKHVQRWAKEIAERPAVK 253

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 27363352 145 VYEAHLSKSKYLAGDFVSLADLAHLPFtdylVGPIGKAYM-IKDRKHVSAWWDDISSRPA 203
Cdd:cd10291  51 VLDRRLAKSKYLAGDEYSIADIAIWPW----VARHEWQGIdLADFPNLKRWFERLAARPA 106

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 27363352   3 LKVYGphFASPKRALVTLIEK---GVAFETIPVDLMKgEHKQPAYLALQPFGTVPAVVDGD-YKIFESRAVMRYVAEK 76
Cdd:cd03044   1 GTLYT--YPGNPRSLKILAAAkynGLDVEIVDFQPGK-ENKTPEFLKKFPLGKVPAFEGADgFCLFESNAIAYYVANL 75

GST_N family, Ganglioside-induced differentiation-associated protein 1 (GDAP1) 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 TRX-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 27363352   1 MVLKVYGPHFASPKRALVtLIEKGVAFETIPVDLMKGEHKQPAYLALQPFGTVPAVVDGDYKIFESRAVMRYV 73
Cdd:cd03052   1 LVLYHWTQSFSSQKVRLV-IAEKGLRCEEYDVSLPLSEHNEPWFMRLNPTGEVPVLIHGDNIICDPTQIIDYL 72

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27363352  94 QVEQWLDVEATTYHPPLLNLTLhimfaSVMGFP-SDEKLIKESEEKLAGVLDVYEAHLSKSKYLAGDFVSLADLAH---- 168
Cdd:cd10294   4 LVWQWVSFADNELTPAACAAAF-----PLLGLSgSDKQNQQRSLAELQRVLKVLDCYLKLRTYLVGEAITLADIAVacal 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 27363352 169 -LPFTDYLVGPIGKAYMikdrkHVSAWWDDISSRPAWKETVAKYS 212
Cdd:cd10294  79 lLPFKYVLDPARRESLL-----NVTRWFLTCVNQPEFLAVLGEVS 118

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 27363352  15 RALVTLIEKGVAFETIPVDLMKGEHKQpAYLALQPFGTVPAVVDGDYKIFESRAVMRYVA 74
Cdd:cd03043  15 RPWLLLKAAGIPFEEILVPLYTPDTRA-RILEFSPTGKVPVLVDGGIVVWDSLAICEYLA 73

C-terminal, alpha helical domain of Class Delta and Epsilon Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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 27363352  92 RGQVEQWLDVEATTYHPPLLNLTLHIMFASVmgFPSDEKLikeseEKLAGVLDVYEAHLSKSKYLAGDFVSLADLA 167
Cdd:cd03177   3 RAIVNQRLFFDSGTLYQRLRDYYYPILFGGA--EPPEEKL-----DKLEEALEFLETFLEGSDYVAGDQLTIADLS 71

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 27363352  11 ASP--KRALVTLIEKG--VAFETIPVDLMKGEhkqPAYLALQPFGTVPAVV-DGDYKIFESRAVMRYV 73
Cdd:cd03049   8 TSPyvRKVRVAAHETGlgDDVELVLVNPWSDD---ESLLAVNPLGKIPALVlDDGEALFDSRVICEYL 72

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27363352   132 IKESEEKLAGVLDVYEAHLSKSKYLAGDFVSLADLAHLPFTDYLVGPIGKAYMIKDRKHVSAW 194
Cdd:pfam13410   2 LERAREQLRAALDALEARLADGPGLLGDRPTLADIALAPVLARLDAAYPGLDLREGYPRLRAW 64

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.

                        10        20
                ....*....|....*....|....*
gi 27363352 147 EAHLSKSKYLAGDFVSLADLAHLPF 171
Cdd:cd03196  54 EARLSQHAYLFGDRPSLADYAIFPF 78

GST_N family, Class Mu 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 class Mu subfamily is composed of eukaryotic GSTs. In rats, at least six distinct class Mu subunits have been identified, with homologous genes in humans for five of these subunits. Class Mu GSTs can form homodimers and heterodimers, giving a large number of possible isoenzymes that can be formed, all with overlapping activities but different substrate specificities. They are the most abundant GSTs in human liver, skeletal muscle and brain, and are believed to provide protection against diseases including cancer and neurodegenerative disorders. Some isoenzymes have additional specific functions. Human GST M1-1 acts as an endogenous inhibitor of ASK1 (apoptosis signal-regulating kinase 1), thereby suppressing ASK1-mediated cell death. Human GSTM2-2 and 3-3 have been identified as prostaglandin E2 synthases in the brain and may play crucial roles in temperature and sleep-wake regulation.

                        10        20
                ....*....|....*....|....*....
gi 27363352  49 PFGTVPAVVDGDYKIFESRAVMRYVAEKY 77
Cdd:cd03075  54 DFPNLPYYIDGDVKLTQSNAILRYIARKH 82