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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1204944571   1 MIKLYRYPLSGHSHRVELMLSLLGVPAERVHVDLKQGAHKTPEFLAtLNSFGQVPVIDDNGVVLADSNAILVYLAGQYGT 80
Cdd:COG0625     1 MMKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLA-LNPLGKVPVLVDDGLVLTESLAILEYLAERYPE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1204944571  81 AQWLPTEPLAQARVQRWLSAAAGPLHtgPAAARLITVFGAALDAEAT---ISRSHAFLKVVEHQLEQSRFLTGDLPTIAD 157
Cdd:COG0625    80 PPLLPADPAARARVRQWLAWADGDLH--PALRNLLERLAPEKDPAAIaraRAELARLLAVLEARLAGGPYLAGDRFSIAD 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1204944571 158 IAHYTYIAHAPEGNVALDDYPQVRAWLGSIEALQGFVGMQRTA 200
Cdd:COG0625   158 IALAPVLRRLDRLGLDLADYPNLAAWLARLAARPAFQRALAAA 200

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1204944571   1 MIKLYRYPLSGHSHRVELMLSLLGVPAERVHVDLKQGAHKTPEFLAtLNSFGQVPVIDDNGVVLADSNAILVYLAGQYGT 80
Cdd:COG0625     1 MMKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLA-LNPLGKVPVLVDDGLVLTESLAILEYLAERYPE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1204944571  81 AQWLPTEPLAQARVQRWLSAAAGPLHtgPAAARLITVFGAALDAEAT---ISRSHAFLKVVEHQLEQSRFLTGDLPTIAD 157
Cdd:COG0625    80 PPLLPADPAARARVRQWLAWADGDLH--PALRNLLERLAPEKDPAAIaraRAELARLLAVLEARLAGGPYLAGDRFSIAD 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1204944571 158 IAHYTYIAHAPEGNVALDDYPQVRAWLGSIEALQGFVGMQRTA 200
Cdd:COG0625   158 IALAPVLRRLDRLGLDLADYPNLAAWLARLAARPAFQRALAAA 200

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1204944571   1 MIKLYRyPLSGHSHRVELMLSLLGVPAERVHVDLKQGAHKTPEFLAtLNSFGQVPVIDDNGVVLADSNAILVYLAGQYGT 80
Cdd:PLN02395    2 VLKVYG-PAFASPKRALVTLIEKGVEFETVPVDLMKGEHKQPEYLA-LQPFGVVPVIVDGDYKIFESRAIMRYYAEKYRS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1204944571  81 --AQWLPTEPLAQARVQRWLSAAAGPLHTGPAAARLITVFGAAL---DAEATISRSH----AFLKVVEHQLEQSRFLTGD 151
Cdd:PLN02395   80 qgPDLLGKTIEERGQVEQWLDVEATSYHPPLLNLTLHILFASKMgfpADEKVIKESEeklaKVLDVYEARLSKSKYLAGD 159

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1204944571 152 LPTIADIAH--YTYIAHAPEGNVAL-DDYPQVRAWLGSI 187
Cdd:PLN02395  160 FVSLADLAHlpFTEYLVGPIGKAYLiKDRKHVSAWWDDI 198

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1204944571   1 MIKLYRYPLSGHSHRVELMLSLLGVPAERVHVDLKQGAHKTPEFLAtLNSFGQVPVIDDNGVVLADSNAILVYLAGQYGT 80
Cdd:COG0625     1 MMKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLA-LNPLGKVPVLVDDGLVLTESLAILEYLAERYPE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1204944571  81 AQWLPTEPLAQARVQRWLSAAAGPLHtgPAAARLITVFGAALDAEAT---ISRSHAFLKVVEHQLEQSRFLTGDLPTIAD 157
Cdd:COG0625    80 PPLLPADPAARARVRQWLAWADGDLH--PALRNLLERLAPEKDPAAIaraRAELARLLAVLEARLAGGPYLAGDRFSIAD 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1204944571 158 IAHYTYIAHAPEGNVALDDYPQVRAWLGSIEALQGFVGMQRTA 200
Cdd:COG0625   158 IALAPVLRRLDRLGLDLADYPNLAAWLARLAARPAFQRALAAA 200

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 1204944571   2 IKLYRYPLSGHSHRVELMLSLLGVPAERVHVDLKQGAHKTPEFLAtLNSFGQVPVIDDNGVVLADSNAILVYLA 75
Cdd:cd03056     1 MKLYGFPLSGNCYKVRLLLALLGIPYEWVEVDILKGETRTPEFLA-LNPNGEVPVLELDGRVLAESNAILVYLA 73

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1204944571   2 IKLYRYPLSgHSHRVELMLSLLGVPAERVHVDLKQGAHKTPEFLAtLNSFGQVPVIDDNGVVLADSNAILVYLAGQYG 79
Cdd:cd03046     1 ITLYHLPRS-RSFRILWLLEELGLPYELVLYDRGPGEQAPPEYLA-INPLGKVPVLVDGDLVLTESAAIILYLAEKYG 76

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The class Phi GST subfamily has experience extensive gene duplication. The Arabidopsis and Oryza genomes contain 13 and 16 Phi 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1204944571   2 IKLYRYPLSGHSHRVELMLSLLGVPAERVHVDLKQGAHKTPEFLAtLNSFGQVPVIDDNGVVLADSNAILVYLA 75
Cdd:cd03053     2 LKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTKGEHKSPEHLA-RNPFGQIPALEDGDLKLFESRAITRYLA 74

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 1204944571   2 IKLYRYPLSGHSHRVELMLSLLGVPAERVHVDLKQGAHKTPEFLAtLNSFGQVPVIDDNGVVLADSNAILVYLA 75
Cdd:pfam02798   3 LTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLK-LNPLGKVPALEDGGKKLTESRAILEYIA 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 1204944571   2 IKLYRYPLSGHSHRVELMLSLLGVPAERVHVDLKQGAHKTPEFLAtLNSFGQVPVIDDNGVVLADSNAILVYLA 75
Cdd:cd03045     1 IDLYYLPGSPPCRAVLLTAKALGLELNLKEVNLMKGEHLKPEFLK-LNPQHTVPTLVDNGFVLWESHAILIYLV 73

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1204944571   2 IKLYRYPLSGhSHRVELMLSLLGVPAERVHVDLKQGAHKTPEFLAtLNSFGQVPV-IDDNGVVLADSNAILVYLAGQY 78
Cdd:cd03057     1 MKLYYSPGAC-SLAPHIALEELGLPFELVRVDLRTKTQKGADYLA-INPKGQVPAlVLDDGEVLTESAAILQYLADLH 76

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 1204944571   3 KLYRYPLSGHSHRVELMLSLLGVPAERVHVDLKQGAHKTPEFLAtLNSFGQVPVID-DNGVVLADSNAILVYL 74
Cdd:cd03051     2 KLYDSPTAPNPRRVRIFLAEKGIDVPLVTVDLAAGEQRSPEFLA-KNPAGTVPVLElDDGTVITESVAICRYL 73

GSH-dependent disulfide bond oxidoreductase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1204944571   1 MIKLYRYPlSGHSHRVELMLSLLGVPAERVHVDLKQGAHKTPEFLaTLNSFGQVPVIDDNG-------VVLADSNAILVY 73
Cdd:PRK13972    1 MIDLYFAP-TPNGHKITLFLEEAELDYRLIKVDLGKGGQFRPEFL-RISPNNKIPAIVDHSpadggepLSLFESGAILLY 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1204944571  74 LAGQYGTaqWLPTEPLAQARVQRWL---SAAAGPL-----HTGPAAARLITVFGAALDAEatisrSHAFLKVVEHQLEQS 145
Cdd:PRK13972   79 LAEKTGL--FLSHETRERAATLQWLfwqVGGLGPMlgqnhHFNHAAPQTIPYAIERYQVE-----TQRLYHVLNKRLENS 151

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1204944571 146 RFLTGDLPTIADIAHYTYIAHAPEGNVALDDYPQVRAWLGSIEAlqgfvgmqRTAVGLA 204
Cdd:PRK13972  152 PWLGGENYSIADIACWPWVNAWTRQRIDLAMYPAVKNWHERIRS--------RPATGQA 202

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1204944571   1 MIKLYRYPLSGHSHRVELMLSLLGVPAERVHVDLKQGAHKTPEFLATlNSFGQVPVIDDNGVVLADSNAILVYLAGQY-- 78
Cdd:PLN02473    2 VVKVYGQIKAANPQRVLLCFLEKGIEFEVIHVDLDKLEQKKPEHLLR-QPFGQVPAIEDGDLKLFESRAIARYYATKYad 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1204944571  79 -GTA-------------QWLPTE-----PLAQARVqrwLSAAAGPLHTGPAAARLITVFGAALDaeatisrshAFLKVVE 139
Cdd:PLN02473   81 qGTDllgktlehraivdQWVEVEnnyfyAVALPLV---INLVFKPRLGEPCDVALVEELKVKFD---------KVLDVYE 148

                         170       180
                  ....*....|....*....|.
gi 1204944571 140 HQLEQSRFLTGDLPTIADIAH 160
Cdd:PLN02473  149 NRLATNRYLGGDEFTLADLTH 169

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1204944571   2 IKLYRYPLSGHSHRVELMLSLLGVPAERVHVDLkqgAHKtPEFLATLNSFGQVPVIDDNGVVLADSNAILVYL 74
Cdd:cd03059     1 MTLYSGPDDVYSHRVRIVLAEKGVSVEIIDVDP---DNP-PEDLAELNPYGTVPTLVDRDLVLYESRIIMEYL 69

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        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1204944571 123 DAEATISRSHA--FLKVVEHQLEQSRFLTGDLPTIADIAHYTYI---AHAPEGNVALDDYPQVRAWL 184
Cdd:cd03196    36 EDDEEEYRAQAeeFLAELEARLSQHAYLFGDRPSLADYAIFPFVrqfAHVDRDWFDASPYPNLRRWL 102

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 1204944571  13 SHRVELMLSLLGVPAERVHVDLKqgahkTPEFLATLNSF---GQVPVIDDNGVVLADSNAILVYLA 75
Cdd:cd03043    13 SLRPWLLLKAAGIPFEEILVPLY-----TPDTRARILEFsptGKVPVLVDGGIVVWDSLAICEYLA 73

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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1204944571 136 KVVEHQLEQSRFLTGDLPTIADIAHYTYIAHAPEGNVALDDYPQVRAWLGSIEA 189
Cdd:cd10291    50 GVLDRRLAKSKYLAGDEYSIADIAIWPWVARHEWQGIDLADFPNLKRWFERLAA 103

GST_N family, Class Omega subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. They contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism. Polymorphisms of the class Omega GST genes may be associated with the development of some types of cancer and the age-at-onset of both Alzheimer's and Parkinson's diseases.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1204944571   2 IKLYRYPLSGHSHRVELMLSLLGVPAERVHVDLKqgaHKtPEFLATLNSFGQVPVID-DNGVVLADSNAILVYL 74
Cdd:cd03055    19 IRLYSMRFCPYAQRARLVLAAKNIPHEVININLK---DK-PDWFLEKNPQGKVPALEiDEGKVVYESLIICEYL 88

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 1204944571  93 RVQRWLSAAAGPLHTGPAAARLITVFGAALDAEATISRSHAFLKVVEHQLEQSRFLTGDLPTIADIAHYTYIAHAPEGNV 172
Cdd:cd00299     3 ALEDWADATLAPPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEALGP 82

                          90
                  ....*....|....*
gi 1204944571 173 A---LDDYPQVRAWL 184
Cdd:cd00299    83 YydlLDEYPRLKAWY 97

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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 members include the class II insect GSTs, S-crystallins from cephalopods 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. Also members are novel GSTs from the fungus Cunninghamella elegans, designated as class Gamma, and from the protozoan Blepharisma japonicum, described as a light-inducible GST.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1204944571   2 IKLYRYPLSGHSHRVELMLSLLGVPAE--RVHVDLKQGAHKTPEFLatlnsFGQVPVIDDNGVVLADSNAILVYLA 75
Cdd:cd03039     1 YKLTYFNIRGRGEPIRLLLADAGVEYEdvRITYEEWPELDLKPTLP-----FGQLPVLEIDGKKLTQSNAILRYLA 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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1204944571 135 LKVVEHQLEQSRFLTGDLPTIADIAHYTYIAHAPE--GNVALDDYPQVRAWLGSIEAL 190
Cdd:pfam00043  35 LSALEEVLKGQTYLVGDKLTLADIALAPALLWLYEldPACLREKFPNLKAWFERVAAR 92

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 1204944571   4 LYRYPLSGHSHRVELMLSLLGVPAERVHVDLKQGAHKTPEFLaTLNSFGQVPVIDDNGVVLADSNAILVYL 74
Cdd:cd03052     3 LYHWTQSFSSQKVRLVIAEKGLRCEEYDVSLPLSEHNEPWFM-RLNPTGEVPVLIHGDNIICDPTQIIDYL 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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1204944571 135 LKVVEHQLEQSRFLTGDLPTIADIAHYT---YIAHAPEGNVaLDDYPQVRAWLGSIEA 189
Cdd:cd03187    54 LDVYEARLSKSKYLAGDSFTLADLSHLPnlhYLMATPSKKL-FDSRPHVKAWWEDISA 110

GST_N family, Beta etherase LigE subfamily; composed of proteins similar to Sphingomonas paucimobilis beta etherase, LigE, a GST-like protein that catalyzes the cleavage of the beta-aryl ether linkages present in low-moleculer weight lignins using GSH as the hydrogen donor. This reaction is an essential step in the degradation of lignin, a complex phenolic polymer that is the most abundant aromatic material in the biosphere. The beta etherase activity of LigE is enantioselective and it complements the activity of the other GST family beta etherase, LigF.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1204944571   2 IKLY-------RYPLSGHSHRVELMLSLLGVPAERVHVDLkqgahktPEFLATLNSFGQ-----VPVI-DDNGVVLADSN 68
Cdd:cd03038     1 ITLYdlagkdpVRAFSPNVWKTRLALNHKGLEYKTVPVEF-------PDIPPILGELTSggfytVPVIvDGSGEVIGDSF 73

                          90
                  ....*....|.
gi 1204944571  69 AILVYLAGQYG 79
Cdd:cd03038    74 AIAEYLEEAYP 84

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1204944571 124 AEATISRSHAFLKVVEHQLEQSRFLTGDLPTIADIAHYTYIAHA-------PEGNVALddypqvRAWLGSIEA 189
Cdd:cd03182    46 GERNKKRVIDFLPVLDKRLAESPYVAGDRFSIADITAFVALDFAknlklpvPEELTAL------RRWYERMAA 112

GST_N family, Class Alpha 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 Alpha subfamily is composed of eukaryotic GSTs which can form homodimer and heterodimers. There are at least six types of class Alpha GST subunits in rats, four of which have human counterparts, resulting in many possible isoenzymes with different activities, tissue distribution and substrate specificities. Human GSTA1-1 and GSTA2-2 show high GSH peroxidase activity. GSTA3-3 catalyzes the isomerization of intermediates in steroid hormone biosynthesis. GSTA4-4 preferentially catalyzes the GSH conjugation of alkenals.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1204944571   3 KLYRYPLSGHSHRVELMLSLLGVPAERVHVdlkqgahKTPEFLATLNS-----FGQVPVIDDNGVVLADSNAILVYLAGQ 77
Cdd:cd03077     3 VLHYFNGRGRMESIRWLLAAAGVEFEEKFI-------ESAEDLEKLKKdgslmFQQVPMVEIDGMKLVQTRAILNYIAGK 75

                  .
gi 1204944571  78 Y 78
Cdd:cd03077    76 Y 76

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1204944571   1 MIKLYRYPLSGHSHRVELMLSLLGVPAERVHVDLKQGAHK-TPEFLatlnsFGQVPVIDDNGVVLADSNAILVYLA 75
Cdd:cd03076     1 PYTLTYFPVRGRAEAIRLLLADQGISWEEERVTYEEWQESlKPKML-----FGQLPCFKDGDLTLVQSNAILRHLG 71

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1204944571 125 EATISRSHAFLKVVEHQLEQSRFLTGDLPTIADIA--HYTY------IAHAPegnvalddYPQVRAWLGSIEALQGF 193
Cdd:cd03180    42 AASLAACNKLMAILDAQLARQAYLAGDRFTLADIAlgCSVYrwlelpIERPA--------LPHLERWYARLSQRPAF 110