GSH-dependent disulfide bond oxidoreductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799673     1 MIDLYFAPTPNGHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDHSPADGGEPLSLFESGAILLYLA 80
Cdd:PRK13972   1 MIDLYFAPTPNGHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDHSPADGGEPLSLFESGAILLYLA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799673    81 EKTGLFLSHETRERAATLQWLFWQVGGLGPMLGQNHHFNHAAPQTIPYAIERYQVETQRLYHVLNKRLENSPWLGGENYS 160
Cdd:PRK13972  81 EKTGLFLSHETRERAATLQWLFWQVGGLGPMLGQNHHFNHAAPQTIPYAIERYQVETQRLYHVLNKRLENSPWLGGENYS 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 1799673   161 IADIACWPWVNAWTRQRIDLAMYPAVKNWHERIRSRPATGQALLKAQLGDERSDS 215
Cdd:PRK13972 161 IADIACWPWVNAWTRQRIDLAMYPAVKNWHERIRSRPATGQALLKAQLGDERSDS 215

GSH-dependent disulfide bond oxidoreductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799673     1 MIDLYFAPTPNGHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDHSPADGGEPLSLFESGAILLYLA 80
Cdd:PRK13972   1 MIDLYFAPTPNGHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDHSPADGGEPLSLFESGAILLYLA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799673    81 EKTGLFLSHETRERAATLQWLFWQVGGLGPMLGQNHHFNHAAPQTIPYAIERYQVETQRLYHVLNKRLENSPWLGGENYS 160
Cdd:PRK13972  81 EKTGLFLSHETRERAATLQWLFWQVGGLGPMLGQNHHFNHAAPQTIPYAIERYQVETQRLYHVLNKRLENSPWLGGENYS 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 1799673   161 IADIACWPWVNAWTRQRIDLAMYPAVKNWHERIRSRPATGQALLKAQLGDERSDS 215
Cdd:PRK13972 161 IADIACWPWVNAWTRQRIDLAMYPAVKNWHERIRSRPATGQALLKAQLGDERSDS 215

C-terminal, alpha helical domain of Escherichia coli YfcG Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YfcG-like subfamily; composed of the Escherichia coli YfcG and related proteins. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. YfcG is one of nine GST homologs in Escherichia coli. It is expressed predominantly during the late stationary phase where the predominant form of GSH is glutathionylspermidine (GspSH), suggesting that YfcG might interact with GspSH. It has very low or no GSH transferase or peroxidase activity, but displays a unique disulfide bond reductase activity that is comparable to thioredoxins (TRXs) and glutaredoxins (GRXs). However, unlike TRXs and GRXs, YfcG does not contain a redox active cysteine residue and may use a bound thiol disulfide couple such as 2GSH/GSSG for activity. The crystal structure of YcfG reveals a bound GSSG molecule in its active site. The actual physiological substrates for YfcG are yet to be identified.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799673   93 ERAATLQWLFWQVGGLGPMLGQNHHFNHAAPQTIPYAIERYQVETQRLYHVLNKRLENSPWLGGENYSIADIACWPWVNA 172
Cdd:cd10291   1 ERYAVLQWLMWQMGGLGPMQGQAHHFKRYAPEKIPYAIKRYTNETKRLYGVLDRRLAKSKYLAGDEYSIADIAIWPWVAR 80

                        90       100       110
                ....*....|....*....|....*....|
gi 1799673  173 WTRQRIDLAMYPAVKNWHERIRSRPATGQA 202
Cdd:cd10291  81 HEWQGIDLADFPNLKRWFERLAARPAVQKG 110

GSH-dependent disulfide bond oxidoreductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799673     1 MIDLYFAPTPNGHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDHSPADGGEPLSLFESGAILLYLA 80
Cdd:PRK13972   1 MIDLYFAPTPNGHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDHSPADGGEPLSLFESGAILLYLA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799673    81 EKTGLFLSHETRERAATLQWLFWQVGGLGPMLGQNHHFNHAAPQTIPYAIERYQVETQRLYHVLNKRLENSPWLGGENYS 160
Cdd:PRK13972  81 EKTGLFLSHETRERAATLQWLFWQVGGLGPMLGQNHHFNHAAPQTIPYAIERYQVETQRLYHVLNKRLENSPWLGGENYS 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 1799673   161 IADIACWPWVNAWTRQRIDLAMYPAVKNWHERIRSRPATGQALLKAQLGDERSDS 215
Cdd:PRK13972 161 IADIACWPWVNAWTRQRIDLAMYPAVKNWHERIRSRPATGQALLKAQLGDERSDS 215

C-terminal, alpha helical domain of Escherichia coli YfcG Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YfcG-like subfamily; composed of the Escherichia coli YfcG and related proteins. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. YfcG is one of nine GST homologs in Escherichia coli. It is expressed predominantly during the late stationary phase where the predominant form of GSH is glutathionylspermidine (GspSH), suggesting that YfcG might interact with GspSH. It has very low or no GSH transferase or peroxidase activity, but displays a unique disulfide bond reductase activity that is comparable to thioredoxins (TRXs) and glutaredoxins (GRXs). However, unlike TRXs and GRXs, YfcG does not contain a redox active cysteine residue and may use a bound thiol disulfide couple such as 2GSH/GSSG for activity. The crystal structure of YcfG reveals a bound GSSG molecule in its active site. The actual physiological substrates for YfcG are yet to be identified.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799673   93 ERAATLQWLFWQVGGLGPMLGQNHHFNHAAPQTIPYAIERYQVETQRLYHVLNKRLENSPWLGGENYSIADIACWPWVNA 172
Cdd:cd10291   1 ERYAVLQWLMWQMGGLGPMQGQAHHFKRYAPEKIPYAIKRYTNETKRLYGVLDRRLAKSKYLAGDEYSIADIAIWPWVAR 80

                        90       100       110
                ....*....|....*....|....*....|
gi 1799673  173 WTRQRIDLAMYPAVKNWHERIRSRPATGQA 202
Cdd:cd10291  81 HEWQGIDLADFPNLKRWFERLAARPAVQKG 110

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 1799673   93 ERAATLQWLFWQVGGLGPMLGQNHHFNHAAPQTIPYAIERYQVETQRLYHVLNKRLENSPWLGGENYSIADIACWPWVNA 172
Cdd:cd03178   1 ERAEVLQWLFFQMSGLGPMFGQAGHFLYFAPEKIPYAIERYTDEVKRLYGVLDKRLSDRPYLAGEEYSIADIALYPWTHY 80

                        90       100
                ....*....|....*....|....*..
gi 1799673  173 WTRQRI-DLAMYPAVKNWHERIRSRPA 198
Cdd:cd03178  81 ADLGGFaDLSEYPNVKRWLERIAARPA 107

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 1799673   93 ERAATLQWLFWQVGGlGPMLGQNH-HFNHAAPQTIPYAIERYQVETQRLYHVLNKRLENSPWLGGENYSIADIACWPWVN 171
Cdd:cd10292   1 KRTETLNWLFWQMGS-APYLGGGFgHFYSYAPVKIEYAIDRFTMEAKRQLDVLDRQLATHKYLAGDEYTIADMAIWPWYG 79

                        90       100       110
                ....*....|....*....|....*....|....
gi 1799673  172 AWTRQR-------IDLAMYPAVKNWHERIRSRPA 198
Cdd:cd10292  80 GLALGSlydaaefLDVDEYKHVQRWAKDIAARPA 113

GST_N family, Saccharomyces cerevisiae GTT1-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. cerevisiae GST protein, GTT1, and the Schizosaccharomyces pombe GST-III. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GTT1, a homodimer, exhibits GST activity with standard substrates and associates with the endoplasmic reticulum. Its expression is induced after diauxic shift and remains high throughout the stationary phase. S. pombe GST-III is implicated in the detoxification of various metals.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799673   19 LEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDHspadggePLSLFESGAILLYLAEKTG 84
Cdd:cd03046  18 LEELGLPYELVLYDRGPGEQAPPEYLAINPLGKVPVLVDG-------DLVLTESAAIILYLAEKYG 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799673    4 LY-FAPTPNGHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDHspadggePLSLFESGAILLYLAEK 82
Cdd:cd03053   4 LYgAAMSTCVRRVLLCLEEKGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALEDG-------DLKLFESRAITRYLAEK 76

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 1799673    4 LY-FAPTPNGHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDhspaDGgepLSLFESGAILLYLA 80
Cdd:cd03056   3 LYgFPLSGNCYKVRLLLALLGIPYEWVEVDILKGETRTPEFLALNPNGEVPVLEL----DG---RVLAESNAILVYLA 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799673   19 LEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDhspaDGGEPlsLFESGAILLYLAEK 82
Cdd:cd03057  18 LEELGLPFELVRVDLRTKTQKGADYLAINPKGQVPALVL----DDGEV--LTESAAILQYLADL 75

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 1799673   92 RERAATLQWLFWQVGGLGPMLGQN--HHFNHAAPQTIPYAIERYQVETQRLYHVLNKRLENSPWLGGENYSIADIACWPW 169
Cdd:cd03180   1 AQRALADRWMDWQTSTLNPAFRYAfwGLVRTPPEQRDPAAIAASLAACNKLMAILDAQLARQAYLAGDRFTLADIALGCS 80

                        90       100
                ....*....|....*....|....*....
gi 1799673  170 VNAWTRQRIDLAMYPAVKNWHERIRSRPA 198
Cdd:cd03180  81 VYRWLELPIERPALPHLERWYARLSQRPA 109

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799673    2 IDLYFAP-TPNGHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDHspadggePLSLFESGAILLYLA 80
Cdd:cd03045   1 IDLYYLPgSPPCRAVLLTAKALGLELNLKEVNLMKGEHLKPEFLKLNPQHTVPTLVDN-------GFVLWESHAILIYLV 73

                .
gi 1799673   81 E 81
Cdd:cd03045  74 E 74

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1799673  127 PYAIERYQVETQRLYHVLNKRLENSPWLGGENYSIADIACWPWVnAWTRQ-RIDLAMYPAVKNWHERIRSRP 197
Cdd:cd03206  28 PLDPERARAISHRLLRLLDQHLAGRDWLAGDRPTIADVACYPYI-ALAPEgGVSLEPYPAIRAWLARVEALP 98

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1799673     10 PNGHKITLFLEEAELDYRLIKVDLgKGGQFRPEFLRISPNNKIPAIVDhspaDGGEPLSlfESGAILLYLAEK 82
Cdd:pfam13409   3 PFSHRVRLALEEKGLPYEIELVDL-DPKDKPPELLALNPLGTVPVLVL----PDGTVLT--DSLVILEYLEEL 68

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 1799673   99 QWLFWQVGGLGPMLGQNHHFNHAAPQTIPYAIERYQVETQRLYHVLNKRLENSPWLGGENYSIADIACWPWVNAWTR--- 175
Cdd:cd00299   3 ALEDWADATLAPPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEAlgp 82

                        90
                ....*....|....*...
gi 1799673  176 QRIDLAMYPAVKNWHERI 193
Cdd:cd00299  83 YYDLLDEYPRLKAWYDRL 100

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799673  128 YAiERYQVETQRLY--------HVLNKRLENSPWLGGENYSIADIACWPWVnawtRQ--RIDL-----AMYPAVKNW 189
Cdd:cd03196  30 YA-DRYPEDDEEEYraqaeeflAELEARLSQHAYLFGDRPSLADYAIFPFV----RQfaHVDRdwfdaSPYPNLRRW 101

GST_N family, 2 repeats of the N-terminal domain of soluble GSTs (2 GST_N) subfamily; composed of uncharacterized 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 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799673    1 MIDLY-FAPTPNGHKITLFLEEAELDYRLIKVdlGKGGQFRPEFLRISPNNKIPAIVDhsPADGgepLSLFESGAILLYL 79
Cdd:cd03041   1 PLELYeFEGSPFCRLVREVLTELELDVILYPC--PKGSPKRDKFLEKGGKVQVPYLVD--PNTG---VQMFESADIVKYL 73

                ...
gi 1799673   80 AEK 82
Cdd:cd03041  74 FKT 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 1799673    4 LY-FAPTPNGHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVdhspADGGEPLSlfESGAILLYL 79
Cdd:cd03051   3 LYdSPTAPNPRRVRIFLAEKGIDVPLVTVDLAAGEQRSPEFLAKNPAGTVPVLE----LDDGTVIT--ESVAICRYL 73

C-terminal, alpha helical domain of GTT1-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae GTT1-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. cerevisiae GST protein, GTT1, and the Schizosaccharomyces pombe GST-III. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. GTT1, a homodimer, exhibits GST activity with standard substrates and associates with the endoplasmic reticulum. Its expression is induced after diauxic shift and remains high throughout the stationary phase. S. pombe GST-III is implicated in the detoxification of various metals.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799673   89 HETRERAATLQWLFWQVGGLGPMLGQNHHFNHAAPQTIPYAIE------------RYQVETQRLYHVLNKRLENSPWLGG 156
Cdd:cd03189   3 PDTAEYADYLYWLHFAEGSLMPPLLLKLVFGKIGEAPPPFFRPisrkiadkplqaFINPELKRHLDFLEDHLAKHPYFAG 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 1799673  157 ENYSIADIACWPWVNAWTRQRIDLAMYPAVKNWHERIRSRP 197
Cdd:cd03189  83 DELTAADIMMSFPLEAALARGPLLEQYPNIAAYLERIEARP 123

GST_N family, Class Zeta subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Class Zeta GSTs, also known as maleylacetoacetate (MAA) isomerases, catalyze the isomerization of MAA to fumarylacetoacetate, the penultimate step in tyrosine/phenylalanine catabolism, using GSH as a cofactor. They show little GSH-conjugating activity towards traditional GST substrates but display modest GSH peroxidase activity. They are also implicated in the detoxification of the carcinogen dichloroacetic acid by catalyzing its dechlorination to glyoxylic acid.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 1799673   24 LDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVdhspaDGGEPLSlfESGAILLYL 79
Cdd:cd03042  24 LDYEYVPVNLLKGEQLSPAYRALNPQGLVPTLV-----IDGLVLT--QSLAIIEYL 72

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 1799673   24 LDYRLIKVDLGKGGqFRPEFLRISPNNKIPAIVDhspADGGeplSLFESGAILLYLAEK 82
Cdd:cd03044  24 LDVEIVDFQPGKEN-KTPEFLKKFPLGKVPAFEG---ADGF---CLFESNAIAYYVANL 75

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799673    19 LEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDhspaDGgepLSLFESGAILLYLAEktgLFLSH--------- 89
Cdd:PRK15113  26 LQEKGLPFELKTVDLDAGEHLQPTYQGYSLTRRVPTLQH----DD---FELSESSAIAEYLEE---RFAPPaweriypad 95

                         90
                 ....*....|....
gi 1799673    90 -ETRERAATLQ-WL 101
Cdd:PRK15113  96 lQARARARQIQaWL 109

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 1799673   17 LFLEEAELDYRLIKVDLGkGGQFRPEFLRISPNNKIPAIVDHSpadggepLSLFESGAILLYLA 80
Cdd:cd03043  18 LLLKAAGIPFEEILVPLY-TPDTRARILEFSPTGKVPVLVDGG-------IVVWDSLAICEYLA 73

C-terminal, alpha helical domain of Class Phi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Phi subfamily; composed of plant-specific class Phi GSTs and related fungal and bacterial proteins. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. The class Phi GST subfamily has experience extensive gene duplication. The Arabidopsis and Oryza genomes contain 13 and 16 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Tau GSTs, showing class specificity in substrate preference. Phi enzymes are highly reactive toward chloroacetanilide and thiocarbamate herbicides. Some Phi GSTs have other functions including transport of flavonoid pigments to the vacuole, shoot regeneration and GSH peroxidase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799673   93 ERAATLQWLfwQVgglgpmlgQNHHFNhaaPQTIPYAIERY--------------QVETQRLYHVLN---KRLENSPWLG 155
Cdd:cd03187   2 ERALVEQWL--EV--------EAHQFD---PPASKLVFELVfkpmlglktdeavvEENEAKLKKVLDvyeARLSKSKYLA 68

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 1799673  156 GENYSIADIACWPW----VNAWTRQRIDlaMYPAVKNWHERIRSRPA 198
Cdd:cd03187  69 GDSFTLADLSHLPNlhylMATPSKKLFD--SRPHVKAWWEDISARPA 113

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799673    4 LYFAPT-PNGHKITLFLEEAELDYRLIKVDLGKGGQfrpEFLRISPNNKIPAIVDHSpadggepLSLFESGAILLYLAEK 82
Cdd:cd03059   3 LYSGPDdVYSHRVRIVLAEKGVSVEIIDVDPDNPPE---DLAELNPYGTVPTLVDRD-------LVLYESRIIMEYLDER 72