putative S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021   4 VYYHPSPNPAKVALFLEE------AGLPYEMVPVDTRKGEQFKPEFLAINPNAKTPALTD--GD--VTVFDSNAILLYLA 73
Cdd:PRK11752   47 LYSLGTPNGQKVTIMLEEllalgvKGAEYDAWLIRIGEGDQFSSGFVEINPNSKIPALLDrsGNppIRVFESGAILLYLA 126

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021  74 EKTGQFLPEDTPrARGDMLSWLmFVATGIGPYCGQAV-HFSRFAPEKIPYAINRYAREAERHWGIIDDLLGRRRYMLGDR 152
Cdd:PRK11752  127 EKFGAFLPKDLA-ARTETLNWL-FWQQGSAPFLGGGFgHFYAYAPEKIEYAINRFTMEAKRQLDVLDKQLAEHEYIAGDE 204

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2326040021 153 YTLVDMSVWGWATRLsfAIGDAWP-------EMFPHVKRHLDEISARPAAQRAV 199
Cdd:PRK11752  205 YTIADIAIWPWYGNL--VLGNLYDaaefldvGSYKHVQRWAKEIAERPAVKRGR 256

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 2326040021   2 IKVYYHP-SPNPAKVALFLEEAGLPYEMVPVDTRKGEQFKPEFLAINPNAKTPALTDGDVTVFDSNAILLYLAE 74
Cdd:pfam02798   3 LTLYGIRgSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

putative S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021   4 VYYHPSPNPAKVALFLEE------AGLPYEMVPVDTRKGEQFKPEFLAINPNAKTPALTD--GD--VTVFDSNAILLYLA 73
Cdd:PRK11752   47 LYSLGTPNGQKVTIMLEEllalgvKGAEYDAWLIRIGEGDQFSSGFVEINPNSKIPALLDrsGNppIRVFESGAILLYLA 126

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021  74 EKTGQFLPEDTPrARGDMLSWLmFVATGIGPYCGQAV-HFSRFAPEKIPYAINRYAREAERHWGIIDDLLGRRRYMLGDR 152
Cdd:PRK11752  127 EKFGAFLPKDLA-ARTETLNWL-FWQQGSAPFLGGGFgHFYAYAPEKIEYAINRFTMEAKRQLDVLDKQLAEHEYIAGDE 204

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2326040021 153 YTLVDMSVWGWATRLsfAIGDAWP-------EMFPHVKRHLDEISARPAAQRAV 199
Cdd:PRK11752  205 YTIADIAIWPWYGNL--VLGNLYDaaefldvGSYKHVQRWAKEIAERPAVKRGR 256

GST_N family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p and related GSTs. Ure2p is a regulator for nitrogen catabolism in yeast. It represses the expression of several gene products involved in the use of poor nitrogen sources when rich sources are available. A transmissible conformational change of Ure2p results in a prion called [Ure3], an inactive, self-propagating and infectious amyloid. Ure2p displays a GST fold containing an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The N-terminal TRX-fold domain is sufficient to induce the [Ure3] phenotype and is also called the prion domain of Ure2p. In addition to its role in nitrogen regulation, Ure2p confers protection to cells against heavy metal ion and oxidant toxicity, and shows glutathione (GSH) peroxidase activity. Characterized GSTs in this subfamily include Aspergillus fumigatus GSTs 1 and 2, and Schizosaccharomyces pombe GST-I. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of GSH with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021   1 MIKVYYHPSPNPAKVALFLEEAGLPYEMVPVDTRKGEQFKPEFLAINPNAKTPALTD---GDVTVFDSNAILLYLAEKTG 77
Cdd:cd03048     1 MITLYTHGTPNGFKVSIMLEELGLPYEIHPVDISKGEQKKPEFLKINPNGRIPAIVDhngTPLTVFESGAILLYLAEKYD 80

                  .
gi 2326040021  78 Q 78
Cdd:cd03048    81 K 81

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 2326040021  87 ARGDMLSWLMFVATGIGPYCGQAVHFSRFAPEKIPYAINRYAREAERHWGIIDDLLGRRRYMLGDRYTLVDMSVWGWaTR 166
Cdd:cd03178     1 ERAEVLQWLFFQMSGLGPMFGQAGHFLYFAPEKIPYAIERYTDEVKRLYGVLDKRLSDRPYLAGEEYSIADIALYPW-TH 79

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2326040021 167 LSFAIGDAWPEMFPHVKRHLDEISARPAAQR 197
Cdd:cd03178    80 YADLGGFADLSEYPNVKRWLERIAARPAVQK 110

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021  94 WLMFVATGIGPYCGQAVHFSRFAPEKIPYAINRYAREAERHWGIIDDLLGR--RRYMLGDRYTLVDMSVWGWATRLS--F 169
Cdd:cd10293     8 WLFFQASGQGPYWGQAGWFNVFHAEKVPSAIERYTNEIRRVLGVLETALAEryRVWLVGDKFTIADLAFVPWNNVVDmiF 87

                          90       100       110
                  ....*....|....*....|....*....|
gi 2326040021 170 AIGDAWPEM-FPHVKRHLDEISARPAAQRA 198
Cdd:cd10293    88 IDPELDIKKeFPHVYKWLKRMLARPAVKKA 117

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 2326040021  87 ARGDMLSWLmFVATGIGPYCGQAV-HFSRFAPEKIPYAINRYAREAERHWGIIDDLLGRRRYMLGDRYTLVDMSVWGWAT 165
Cdd:cd10292     1 KRTETLNWL-FWQMGSAPYLGGGFgHFYSYAPVKIEYAIDRFTMEAKRQLDVLDRQLATHKYLAGDEYTIADMAIWPWYG 79

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 2326040021 166 RLSFAIGDAWPEM-----FPHVKRHLDEISARPAAQR 197
Cdd:cd10292    80 GLALGSLYDAAEFldvdeYKHVQRWAKDIAARPAVKR 116

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 2326040021   2 IKVYYHP-SPNPAKVALFLEEAGLPYEMVPVDTRKGEQFKPEFLAINPNAKTPALTDGDVTVFDSNAILLYLA 73
Cdd:cd03056     1 MKLYGFPlSGNCYKVRLLLALLGIPYEWVEVDILKGETRTPEFLALNPNGEVPVLELDGRVLAESNAILVYLA 73

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 2326040021   2 IKVYYHPSPNPAK-VALFLEEAGLPYEMVPVDTRKGEQFKPEFLAINPNAKTPALTDGDVTVFDSNAILLYLAEK 75
Cdd:cd03050     1 LKLYYDLMSQPSRaVYIFLKLNKIPFEECPIDLRKGEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARK 75

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 2326040021   2 IKVYYHP-SPNPAKVALFLEEAGLPYEMVPVDTRKGEQFKPEFLAINPNAKTPALTDGDVTVFDSNAILLYLAE 74
Cdd:cd03045     1 IDLYYLPgSPPCRAVLLTAKALGLELNLKEVNLMKGEHLKPEFLKLNPQHTVPTLVDNGFVLWESHAILIYLVE 74

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021  14 KVALFLEeaGLPYEMVPVD-TRKGEQFKPEFLAINPNAKTPALTDGDVTVFDSNAILLYLAEKTGQ--FLPEDTP-RARG 89
Cdd:TIGR01262  15 RIALALK--GIDYEYVPVNlLRDGEQRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETYPDppLLPADPIkRARV 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021  90 DMLSWLmfVATGIGPYCGQAVhfSRFAPEKI---PYAINRYAreaeRHW---GI--IDDLLG--RRRYMLGDRYTLVDMS 159
Cdd:TIGR01262  93 RALALL--IACDIHPLNNLRV--LQYLREKLgveEEARNRWY----QHWiskGFaaLEALLQphAGRFCVGDTPTLADLC 164

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 2326040021 160 ----VWGwATRLSFAIGDawpemFPHVKRHLDEISARPAAQRA 198
Cdd:TIGR01262 165 lvpqVYN-AERFGVDLTP-----YPTLRRIAAALAALPAFQRA 201

GST_N family, unknown subfamily 2; composed of uncharacterized bacterial proteins with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The sequence from Burkholderia cepacia was identified as part of a gene cluster involved in the degradation of 2,4,5-trichlorophenoxyacetic acid. Some GSTs (e.g. Class Zeta and Delta) are known to catalyze dechlorination reactions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2326040021   9 SPNPAKVALFLEEAGLPYEMVPVDTRKGEQFKPEFLAINPNAKTPALTDGDVTVFDSNAILLYLA 73
Cdd:cd03047     9 SINVQKVLWLLDELGLPYERIDAGGQFGGLDTPEFLAMNPNGRVPVLEDGDFVLWESNAILRYLA 73

glutathionine S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021   2 IKVYYHPSPNPAKVALFLEEAGLPYEMVPVDTRK-----GEqfkpEFLAINPNAKTPALT-DGDVTVFDSNAILLYLAEK 75
Cdd:PRK10542    1 MKLFYKPGACSLASHITLRESGLDFTLVSVDLAKkrlenGD----DYLAINPKGQVPALLlDDGTLLTEGVAIMQYLADS 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021  76 TG--QFLPEDTPRARGDMLSWLMFVAT----GIGPYcgqavhFSRFAPEKI-PYAINRYareaERHWGIIDDLLGRRRYM 148
Cdd:PRK10542   77 VPdrQLLAPVGSLSRYHTIEWLNYIATelhkGFTPL------FRPDTPEEYkPTVRAQL----EKKFQYVDEALADEQWI 146

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2326040021 149 LGDRYTLVD---MSVWGWATRLSFAIGDawpemFPHVKRHLDEISARPAAQRAVA 200
Cdd:PRK10542  147 CGQRFTIADaylFTVLRWAYAVKLNLEG-----LEHIAAYMQRVAERPAVAAALK 196

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021  86 RARGDMLSWLMFVATGIgpycgQAVHFSRFAPEKipYAINRYAREA--------ERHWGIIDDLLGRRRYMLGDRYTLVD 157
Cdd:cd03188     1 LERARLLEWLNFIASEL-----HKAFGPLFYPAR--WADDALAEEVkaaarerlERRLAYLDAQLAGGPYLLGDQFSVAD 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2326040021 158 -----MSVWGWATRLSfaigdawPEMFPHVKRHLDEISARPAAQRA 198
Cdd:cd03188    74 aylfvVLRWARAVGLD-------LSDWPHLAAYLARVAARPAVQAA 112

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021   1 MIKVYYH-PSPNPAKVALFLEEAGLPYEMVPVDTRKGEQFKPEFLAINPNAKTPALTDGDVTVFDSNAILLYLAEK---T 76
Cdd:PLN02473    2 VVKVYGQiKAANPQRVLLCFLEKGIEFEVIHVDLDKLEQKKPEHLLRQPFGQVPAIEDGDLKLFESRAIARYYATKyadQ 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021  77 GQFLPEDTPRARGDMLSWLmfvatgigpycgqAVHFSRFAPEKIPYAINRYAR-------------EAERHWGIIDDLLG 143
Cdd:PLN02473   82 GTDLLGKTLEHRAIVDQWV-------------EVENNYFYAVALPLVINLVFKprlgepcdvalveELKVKFDKVLDVYE 148

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2326040021 144 RR----RYMLGDRYTLVDMS-VWGWATRLSFAIGDAWPEMFPHVKRHLDEISARPAAQRAVAL 201
Cdd:PLN02473  149 NRlatnRYLGGDEFTLADLThMPGMRYIMNETSLSGLVTSRENLNRWWNEISARPAWKKLMEL 211

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 2326040021  85 PRARGDmlSWLMFVATGIGPYCGQA-VHFSRFAPEK-IPYAINRYAREAERHWGIIDDLLGRRRYMLGDRYTLVDM---- 158
Cdd:cd03180     2 QRALAD--RWMDWQTSTLNPAFRYAfWGLVRTPPEQrDPAAIAASLAACNKLMAILDAQLARQAYLAGDRFTLADIalgc 79

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2326040021 159 SVWGWatrlsFAIGDAWPEMfPHVKRHLDEISARPA 194
Cdd:cd03180    80 SVYRW-----LELPIERPAL-PHLERWYARLSQRPA 109

glutathione transferase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021  19 LEEAGLPYEMVPVDTRKGEQFKPEFLAINPNAKTPALTDGDVTVFDSNAILLYLAEK-----TGQFLPED-TPRARGDML 92
Cdd:PRK15113   26 LQEKGLPFELKTVDLDAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEERfappaWERIYPADlQARARARQI 105

                  ....
gi 2326040021  93 -SWL 95
Cdd:PRK15113  106 qAWL 109

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 2326040021  94 WLMFVATGIGPYCGQAVHFSRFAPEKIPYAINRYAREAERHWGIIDDLLGRRRYMLGDRYTLVDMSVWGWATRL-SFAIG 172
Cdd:cd00299     4 LEDWADATLAPPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLeALGPY 83

                          90
                  ....*....|....*
gi 2326040021 173 DAWPEMFPHVKRHLD 187
Cdd:cd00299    84 YDLLDEYPRLKAWYD 98

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2326040021  22 AGLPYEMVpVDTRKGEQFKPEFLAINPNAKTPAL-TDGDVTVFDSNAILLYLAEK 75
Cdd:cd03044    22 NGLDVEIV-DFQPGKENKTPEFLKKFPLGKVPAFeGADGFCLFESNAIAYYVANL 75

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2326040021 139 DDLLGRRRYMLGDRYTLVDMSVWGWatrLSFA--IGDAWPEMFPHVKRHLDEISARPAA 195
Cdd:cd03182    61 DKRLAESPYVAGDRFSIADITAFVA---LDFAknLKLPVPEELTALRRWYERMAARPSA 116

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 2326040021  91 MLSWLMFVATGIGPYCGQAVHFSRFAPEKIPYAINRYAREAERHWGIIDDLLGRRRYMLGDRYTLVDM---SVWGWATRl 167
Cdd:cd03207     1 YLRWLFFAAGTVEPPLLNKALGRFFEPPWGEPAIAAAYGDLDERLAALEAALAGRPYLVGERFSAADLllaSVLRWARA- 79

                          90       100
                  ....*....|....*....|....*..
gi 2326040021 168 sFAIGDAWPEmfphVKRHLDEISARPA 194
Cdd:cd03207    80 -FGLLPEYPA----LRAYVARCTARPA 101

GST_N family, Metaxin subfamily; composed of metaxins and related proteins. Metaxin 1 is a component of a preprotein import complex of the mitochondrial outer membrane. It extends to the cytosol and is anchored to the mitochondrial membrane through its C-terminal domain. In mice, metaxin is required for embryonic development. In humans, alterations in the metaxin gene may be associated with Gaucher disease. Metaxin 2 binds to metaxin 1 and may also play a role in protein translocation into the mitochondria. Genome sequencing shows that a third metaxin gene also exists in zebrafish, Xenopus, chicken and mammals. Sequence analysis suggests that all three metaxins share a common ancestry and that they possess similarity to GSTs. Also included in the subfamily are uncharacterized proteins with similarity to metaxins, including a novel GST from Rhodococcus with toluene o-monooxygenase and glutamylcysteine synthetase activities.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021   8 PSPNPA--KVALFLEEAGLPYEMVPVDtrkgeqfkpeFLAINPNAKTPALTDGDVTVFDSNAILLYLAEK 75
Cdd:cd03054    13 PSLSPEclKVETYLRMAGIPYEVVFSS----------NPWRSPTGKLPFLELNGEKIADSEKIIEYLKKK 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 2326040021 112 FSRFAPEKIPYAINRyaREAERHWGIIDDLLGRRRYMLGDRYTLVDM---SVWGWATRLSFAIGdawPEMFPHVKRHLDE 188
Cdd:pfam00043  14 VPPEEKKEPEVDEAL--EKVARVLSALEEVLKGQTYLVGDKLTLADIalaPALLWLYELDPACL---REKFPNLKAWFER 88

                  ....*
gi 2326040021 189 ISARP 193
Cdd:pfam00043  89 VAARP 93

GST_N family, Class Tau subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The plant-specific class Tau GST subfamily has undergone extensive gene duplication. The Arabidopsis and Oryza genomes contain 28 and 40 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Phi GSTs, showing class specificity in substrate preference. Tau enzymes are highly efficient in detoxifying diphenylether and aryloxyphenoxypropionate herbicides. In addition, Tau GSTs play important roles in intracellular signalling, biosynthesis of anthocyanin, responses to soil stresses and responses to auxin and cytokinin hormones.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2326040021   8 PSPNPAKVALFLEEAGLPYEMVPVD-TRKGEQfkpeFLAINP-NAKTPALTDGDVTVFDSNAILLYLAE 74
Cdd:cd03058     8 ASPFVLRVRIALALKGVPYEYVEEDlGNKSEL----LLASNPvHKKIPVLLHNGKPICESLIIVEYIDE 72

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2326040021 142 LGRRRYMLGDRYTLVDMSVWGWATRLSfaiGDAWPEMF---PHVKRHLDEISARPAAQRAV 199
Cdd:cd03187    61 LSKSKYLAGDSFTLADLSHLPNLHYLM---ATPSKKLFdsrPHVKAWWEDISARPAWKKVL 118

Glutathione S-transferase N-terminal domain; This domain is homologous to pfam02798.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2326040021  10 PNPAKVALFLEEAGLPYEMVPVDTrkgeqfkpEFLAinPNAKTPALTDGDVTVFDSNAILLYLAEKtgqFLPED---TPR 86
Cdd:pfam17172   1 PFCLKVETYLRMAGIPYEVEPSSN--------PSAS--PKGKLPFIELNGDLIADSEFIIEFLKEK---GVDLDaglSPE 67

                  ....*...
gi 2326040021  87 ARGDMLSW 94
Cdd:pfam17172  68 QKADARAL 75