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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 505383088   1 MLTVHHLNQS-RSHRVLWALEELGLTYEIVRYQREKSMLAPDSLKKVHPLGKSPVLEDNGLVLAESGAILEYLQETYDSA 79
Cdd:COG0625    1 MMKLYGSPPSpNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPEP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 505383088  80 sRFKPLDPTHKVQYRFWLHYAEGSLMPLLLMklVFNSLGKPPVPFglrtlgkalgqgvQKAYLNRQLETHARFINDHLAE 159
Cdd:COG0625   81 -PLLPADPAARARVRQWLAWADGDLHPALRN--LLERLAPEKDPA-------------AIARARAELARLLAVLEARLAG 144

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 505383088 160 NSWFAGDTLTMADIQMsFPLFALLARGGID--NLDHIAAWKQRVEARPGWQTTLAKGGPL 217
Cdd:COG0625  145 GPYLAGDRFSIADIAL-APVLRRLDRLGLDlaDYPNLAAWLARLAARPAFQRALAAAEPD 203

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 505383088   1 MLTVHHLNQS-RSHRVLWALEELGLTYEIVRYQREKSMLAPDSLKKVHPLGKSPVLEDNGLVLAESGAILEYLQETYDSA 79
Cdd:COG0625    1 MMKLYGSPPSpNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPEP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 505383088  80 sRFKPLDPTHKVQYRFWLHYAEGSLMPLLLMklVFNSLGKPPVPFglrtlgkalgqgvQKAYLNRQLETHARFINDHLAE 159
Cdd:COG0625   81 -PLLPADPAARARVRQWLAWADGDLHPALRN--LLERLAPEKDPA-------------AIARARAELARLLAVLEARLAG 144

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 505383088 160 NSWFAGDTLTMADIQMsFPLFALLARGGID--NLDHIAAWKQRVEARPGWQTTLAKGGPL 217
Cdd:COG0625  145 GPYLAGDRFSIADIAL-APVLRRLDRLGLDlaDYPNLAAWLARLAARPAFQRALAAAEPD 203

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 505383088    5 HHLNQSRSHRVLWALEELGLTYEIVRYQREKSMLAPDSLKKVHPLGKSPVLEDNGLVLAESGAILEYL 72
Cdd:pfam02798   7 GIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYI 74

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 505383088   1 MLTVHHLNQS-RSHRVLWALEELGLTYEIVRYQREKSMLAPDSLKKVHPLGKSPVLEDNGLVLAESGAILEYLQETYDSA 79
Cdd:COG0625    1 MMKLYGSPPSpNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPEP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 505383088  80 sRFKPLDPTHKVQYRFWLHYAEGSLMPLLLMklVFNSLGKPPVPFglrtlgkalgqgvQKAYLNRQLETHARFINDHLAE 159
Cdd:COG0625   81 -PLLPADPAARARVRQWLAWADGDLHPALRN--LLERLAPEKDPA-------------AIARARAELARLLAVLEARLAG 144

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 505383088 160 NSWFAGDTLTMADIQMsFPLFALLARGGID--NLDHIAAWKQRVEARPGWQTTLAKGGPL 217
Cdd:COG0625  145 GPYLAGDRFSIADIAL-APVLRRLDRLGLDlaDYPNLAAWLARLAARPAFQRALAAAEPD 203

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 505383088   2 LTVHHLNQSRSHRVLWALEELGLTYEIVRYQREKSMLAPDSLKKVHPLGKSPVLEDNGLVLAESGAILEYLQETYD 77
Cdd:cd03046    1 ITLYHLPRSRSFRILWLLEELGLPYELVLYDRGPGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEKYG 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 505383088   2 LTVHHLNQS-RSHRVLWALEELGLTYEIVRYQREKSMlaPDSLKKVHPLGKSPVLEDNGLVLAESGAILEYL 72
Cdd:cd00570    1 LKLYYFPGSpRSLRVRLALEEKGLPYELVPVDLGEGE--QEEFLALNPLGKVPVLEDGGLVLTESLAILEYL 70

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 505383088   1 MLTVHHLNQSRSHRVLWALEELGLTYEIVRYQ-REKSMLAPDSLKkVHPLGKSPVLEDN---GLVLAESGAILEYLQETY 76
Cdd:cd03048    1 MITLYTHGTPNGFKVSIMLEELGLPYEIHPVDiSKGEQKKPEFLK-INPNGRIPAIVDHngtPLTVFESGAILLYLAEKY 79

                 .
gi 505383088  77 D 77
Cdd:cd03048   80 D 80

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 505383088   2 LTVHHLNQS-RSHRVLWALEELGLTYEIVRYQREKSMLAPDSLKKVHPLGKSPVLEDNGLVLAESGAILEYL 72
Cdd:cd03056    1 MKLYGFPLSgNCYKVRLLLALLGIPYEWVEVDILKGETRTPEFLALNPNGEVPVLELDGRVLAESNAILVYL 72

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 505383088  14 RVLWALEELGLTYEIVRYQREKSMLAPDSLKKVHPLGKSPVLEDNGLVLAESGAILEYLQE 74
Cdd:cd03053   15 RVLLCLEEKGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAE 75

GST_N family, Class Beta subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit limited GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they also bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 505383088  17 WALEELGLTYEIVRYQ-REKSMLAPDsLKKVHPLGKSPVLE-DNGLVLAESGAILEYLQETY 76
Cdd:cd03057   16 IALEELGLPFELVRVDlRTKTQKGAD-YLAINPKGQVPALVlDDGEVLTESAAILQYLADLH 76

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 505383088  96 WLHYAEGSLMPLLLMKLVFNSLGKPPVPFGLRtlgKALgQGVQKAYlnrqlethaRFINDHLAENSWFAGDTLTMADIQm 175
Cdd:cd03178    8 WLFFQMSGLGPMFGQAGHFLYFAPEKIPYAIE---RYT-DEVKRLY---------GVLDKRLSDRPYLAGEEYSIADIA- 73

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 505383088 176 SFPLFALLARGGIDNLD---HIAAWKQRVEARPGWQ 208
Cdd:cd03178   74 LYPWTHYADLGGFADLSeypNVKRWLERIAARPAVQ 109

C-terminal, alpha helical domain of an unknown subfamily 7 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 7; composed of uncharacterized proteins with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 505383088 151 RFINDHLAENSWFAGDTLTMADIQMsFPLFALLARGGIDNLD--HIAAWKQRVEARPG 206
Cdd:cd03206   43 RLLDQHLAGRDWLAGDRPTIADVAC-YPYIALAPEGGVSLEPypAIRAWLARVEALPG 99

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 505383088  13 HRVLWALEELGLTYEIVRYQREK-SMLAPDSLKKvHPLGKSPVLEDNGLVLAESGAILEYLQETY-DSASRFKPLDPTHK 90
Cdd:PLN02473  15 QRVLLCFLEKGIEFEVIHVDLDKlEQKKPEHLLR-QPFGQVPAIEDGDLKLFESRAIARYYATKYaDQGTDLLGKTLEHR 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 505383088  91 VQYRFWLHyAEGSLMPLLLMKLVFNSLGKPpvpfglrTLGK----ALGQGVqKAYLNRQLETHarfiNDHLAENSWFAGD 166
Cdd:PLN02473  94 AIVDQWVE-VENNYFYAVALPLVINLVFKP-------RLGEpcdvALVEEL-KVKFDKVLDVY----ENRLATNRYLGGD 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 505383088 167 TLTMADIQ----MSFPLFALLARGGIDNLDHIAAWKQRVEARPGWQTTLAKGG 215
Cdd:PLN02473 161 EFTLADLThmpgMRYIMNETSLSGLVTSRENLNRWWNEISARPAWKKLMELAA 213

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 505383088  10 SRSHRVLWALEELGLTYEIVRYQREKSMLAPDSLKKVHPLGKSPVLEDNGLVLAESGAILEYL 72
Cdd:cd03042   10 SASYRVRIALNLKGLDYEYVPVNLLKGEQLSPAYRALNPQGLVPTLVIDGLVLTQSLAIIEYL 72

putative S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 505383088  45 KVHPLGKSPVLEDNG----LVLAESGAILEYLQETYDsasRFKPLDPTHKVQYRFWLHYAEGSlmplllmklvfnslgkp 120
Cdd:PRK11752  94 EINPNSKIPALLDRSgnppIRVFESGAILLYLAEKFG---AFLPKDLAARTETLNWLFWQQGS----------------- 153

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 505383088 121 pVPFglrtlgkaLGQGVQKAY----------LNR-QLETHARF--INDHLAENSWFAGDTLTMADIQMsFPLFALLARGG 187
Cdd:PRK11752 154 -APF--------LGGGFGHFYayapekieyaINRfTMEAKRQLdvLDKQLAEHEYIAGDEYTIADIAI-WPWYGNLVLGN 223

                        170       180       190
                 ....*....|....*....|....*....|
gi 505383088 188 IDN----LD-----HIAAWKQRVEARPGWQ 208
Cdd:PRK11752 224 LYDaaefLDvgsykHVQRWAKEIAERPAVK 253

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 505383088  12 SHRVLWALEELGLTYEIVRYQREKSmlaPDSLKKVHPL-GKSPVLEDNGLVLAESGAILEYLQETY 76
Cdd:cd03058   12 VLRVRIALALKGVPYEYVEEDLGNK---SELLLASNPVhKKIPVLLHNGKPICESLIIVEYIDEAW 74

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 505383088  15 VLWALEELGLTYEIvryqREKSMLAPDSLK----KVHPLGKSPVLEDNGLVLAESGAILEYLQE 74
Cdd:cd03045   15 VLLTAKALGLELNL----KEVNLMKGEHLKpeflKLNPQHTVPTLVDNGFVLWESHAILIYLVE 74

stringent starvation protein A; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 505383088  12 SHRVLWALEELGLTYEIVryQREKSMLaPDSLKKVHPLGKSPVLEDNGLVLAESGAILEYLQEtydsasRF--KPLDPTH 89
Cdd:PRK09481  22 SHQVRIVLAEKGVSVEIE--QVEKDNL-PQDLIDLNPYQSVPTLVDRELTLYESRIIMEYLDE------RFphPPLMPVY 92

                         90
                 ....*....|....*
gi 505383088  90 KV---QYRFWLHYAE 101
Cdd:PRK09481  93 PVargESRLMMHRIE 107

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
                 ....*....|....*....|....*....|...
gi 505383088  44 KKVHPLGKSPVLEDNGLVLAESGAILEYLQETY 76
Cdd:cd03050   44 KKINPFGKVPAIVDGDFTLAESVAILRYLARKF 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 505383088  14 RVLWALEELGLTYEIVRYQ-REKSMLAPDSLKKvHPLGKSPVLE-DNGLVLAESGAILEYL 72
Cdd:cd03051   14 RVRIFLAEKGIDVPLVTVDlAAGEQRSPEFLAK-NPAGTVPVLElDDGTVITESVAICRYL 73

C-terminal, alpha helical domain of Escherichia coli Yghu Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YghU-like subfamily; composed of the Escherichia coli YghU and related proteins. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. YghU is one of nine GST homologs in the genome of Escherichia coli. It is similar to Escherichia coli YfcG in that it has poor GSH transferase activity towards typical substrates. It shows modest reductase activity towards some organic hydroperoxides. Like YfcG, YghU also shows good disulfide bond oxidoreductase activity comparable to the activities of glutaredoxins and thioredoxins. YghU does not contain a redox active cysteine residue, and may use a bound thiol disulfide couple such as 2GSH/GSSG for activity. The crystal structure of YghU reveals two GSH molecules bound in its active site.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 505383088 144 RQLETharfINDHLAENSWFAGDTLTMADIQMsFPLFALLARGGIDN----LD-----HIAAWKQRVEARPGWQ 208
Cdd:cd10292   47 RQLDV----LDRQLATHKYLAGDEYTIADMAI-WPWYGGLALGSLYDaaefLDvdeykHVQRWAKDIAARPAVK 115

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 505383088  139 KAYLNRQLETHAR---FINDHLAENSWFAGDTLTMADIQMSFPLFALLARG---GIDNLDHIAAWKQRVEARP 205
Cdd:pfam00043  21 EPEVDEALEKVARvlsALEEVLKGQTYLVGDKLTLADIALAPALLWLYELDpacLREKFPNLKAWFERVAARP 93

C-terminal, alpha helical domain of GTT2-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the Saccharomyces cerevisiae GST protein, GTT2. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. GTT2, a homodimer, exhibits GST activity with standard substrates. Strains with deleted GTT2 genes are viable but exhibit increased sensitivity to heat shock.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 505383088 144 RQLETHARFI---NDHLAENSWFAGDTLTMADIQ-MSFPLFALLARGGI-DNLDHIAAWKQRVEARPG 206
Cdd:cd03182   48 RNKKRVIDFLpvlDKRLAESPYVAGDRFSIADITaFVALDFAKNLKLPVpEELTALRRWYERMAARPS 115

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 505383088   37 MLAPDSLKKVHPLGKSPVLEDNGLVLAESGAILEYLQETYDSASrfKPLDPTHKVQYRFWLHYAEGSLMPLLL 109
Cdd:pfam17172  18 EVEPSSNPSASPKGKLPFIELNGDLIADSEFIIEFLKEKGVDLD--AGLSPEQKADARALKALVEEHLYWALL 88

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
                 ....*....|....*....|....*....|....
gi 505383088  40 PDSLKKVHPLGKSPVLE-DNGLVLAESGAILEYL 72
Cdd:cd03055   55 PDWFLEKNPQGKVPALEiDEGKVVYESLIICEYL 88

Glutathione S-transferase C-terminal-like, alpha helical domain of Cysteinyl-tRNA synthetase from higher eukaryotes; Glutathione S-transferase (GST) C-terminal domain family, Cysteinyl-tRNA synthetase (CysRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of CysRS from higher eukaryotes. 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. The GST_C-like domain of CysRS 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. CysRSs from prokaryotes and lower eukaryotes do not appear to contain this GST_C-like domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 505383088 150 ARFINDHLAENSWFAGDTLTMADIQMsfplFALLARGGIDNLDHIAAWKQRVEA 203
Cdd:cd10310   23 AEALNEYLSTRSYLQGFGPSQADVEV----FRLLSRPPADRLVHVLRWYRHIEA 72

Glutathione S-transferase C-terminal-like, alpha helical domain of various Aminoacyl-tRNA synthetases and similar domains; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl-tRNA synthetase (AaRS)-like subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of some eukaryotic AaRSs, as well as similar domains found in proteins involved in protein synthesis including Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 2 (AIMP2), AIMP3, and eukaryotic translation Elongation Factor 1 beta (eEF1b). 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. AaRSs in this subfamily include GluRS from lower eukaryotes, as well as GluProRS, MetRS, and CysRS from higher eukaryotes. AIMPs are non-enzymatic cofactors that play critical roles in the assembly and formation of a macromolecular multi-tRNA synthetase protein complex found in higher eukaryotes. The GST_C-like domain is involved in protein-protein interactions, mediating the formation of aaRS complexes such as the MetRS-Arc1p-GluRS ternary complex in lower eukaryotes and the multi-aaRS complex in higher eukaryotes, that act as molecular hubs for protein synthesis. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 505383088 144 RQLETHARFINDHLAENSWFAGDTLTMADIQmsfpLFALLAR 185
Cdd:cd10289   19 KELEALLKSLNSYLASRTFLVGYSLTLADVA----VFSALYP 56

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 505383088 153 INDHLAE--NSWFAGDTLTMADiqMSF-PLFALLARGGIDNLD-------HIAAWKQRVEARPGWQTT 210
Cdd:cd10293   52 LETALAEryRVWLVGDKFTIAD--LAFvPWNNVVDMIFIDPELdikkefpHVYKWLKRMLARPAVKKA 117