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 15218641 128 KTMGTQRMWMAIESFEFDPLTSTLTWEQSIKPMYGLKTDYKVVNETEAKLEKVLDIYEERLKNSSFLASNSFTMADLYHL 207
Cdd:cd03187   1 KERALVEQWLEVEAHQFDPPASKLVFELVFKPMLGLKTDEAVVEENEAKLKKVLDVYEARLSKSKYLAGDSFTLADLSHL 80

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 15218641 208 PNIQYLMDTHTKRMFVNRPSVRRWVAEITARPAWKRAC 245
Cdd:cd03187  81 PNLHYLMATPSKKLFDSRPHVKAWWEDISARPAWKKVL 118

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 15218641 128 KTMGTQRMWMAIESFEFDPLTSTLTWEQSIKPMYGLKTDYKVVNETEAKLEKVLDIYEERLKNSSFLASNSFTMADLYHL 207
Cdd:cd03187   1 KERALVEQWLEVEAHQFDPPASKLVFELVFKPMLGLKTDEAVVEENEAKLKKVLDVYEARLSKSKYLAGDSFTLADLSHL 80

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 15218641 208 PNIQYLMDTHTKRMFVNRPSVRRWVAEITARPAWKRAC 245
Cdd:cd03187  81 PNLHYLMATPSKKLFDSRPHVKAWWEDISARPAWKKVL 118

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218641  39 YKIYGYPYSTNTRRVLAVLHEKGLSYDPITVNLIAGDQKKPSFLAINPFGQVPVFLDGGLKLTESRAISEYIATVHksRG 118
Cdd:COG0625   2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERY--PE 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218641 119 TQLLNyKSYKTMGTQRMWMAIESFEFDPLTSTLTWeqsikpMYGLKTDYKVVNETEAKLEKVLDIYEERLKNSSFLASNS 198
Cdd:COG0625  80 PPLLP-ADPAARARVRQWLAWADGDLHPALRNLLE------RLAPEKDPAAIARARAELARLLAVLEARLAGGPYLAGDR 152

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 15218641 199 FTMADLYHLPNIQYLMdtHTKRMFVNRPSVRRWVAEITARPAWKRA 244
Cdd:COG0625 153 FSIADIALAPVLRRLD--RLGLDLADYPNLAAWLARLAARPAFQRA 196

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 15218641    39 YKIYGYPYSTNTRRVLAVLHEKGLSYDPITVNLIAGDQKKPSFLAINPFGQVPVFLDGGLKLTESRAISEYIA 111
Cdd:pfam02798   3 LTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIA 75

glutathione transferase;

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 15218641   53 VLAVLHEKGLSYDPITVNLIAGDQKKPSFLAINPFGQVPVFLDGGLKLTESRAISEY 109
Cdd:PRK15113  22 AFVALQEKGLPFELKTVDLDAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEY 78

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 15218641 128 KTMGTQRMWMAIESFEFDPLTSTLTWEQSIKPMYGLKTDYKVVNETEAKLEKVLDIYEERLKNSSFLASNSFTMADLYHL 207
Cdd:cd03187   1 KERALVEQWLEVEAHQFDPPASKLVFELVFKPMLGLKTDEAVVEENEAKLKKVLDVYEARLSKSKYLAGDSFTLADLSHL 80

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 15218641 208 PNIQYLMDTHTKRMFVNRPSVRRWVAEITARPAWKRAC 245
Cdd:cd03187  81 PNLHYLMATPSKKLFDSRPHVKAWWEDISARPAWKKVL 118

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218641   40 KIYGYPYSTNTRRVLAVLHEKGLSYDPITVNLIAGDQKKPSFLAINPFGQVPVFLDGGLKLTESRAISEYIATVHKSRGT 119
Cdd:PLN02473   4 KVYGQIKAANPQRVLLCFLEKGIEFEVIHVDLDKLEQKKPEHLLRQPFGQVPAIEDGDLKLFESRAIARYYATKYADQGT 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218641  120 QLLNyKSYKTMGTQRMWMAIESFEFDPLTSTLTWEQSIKPMYGLKTDYKVVNETEAKLEKVLDIYEERLKNSSFLASNSF 199
Cdd:PLN02473  84 DLLG-KTLEHRAIVDQWVEVENNYFYAVALPLVINLVFKPRLGEPCDVALVEELKVKFDKVLDVYENRLATNRYLGGDEF 162

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 15218641  200 TMADLYHLPNIQYLMD-THTKRMFVNRPSVRRWVAEITARPAWKR 243
Cdd:PLN02473 163 TLADLTHMPGMRYIMNeTSLSGLVTSRENLNRWWNEISARPAWKK 207

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 15218641  40 KIYGYPYSTNTRRVLAVLHEKGLSYDPITVNLIAGDQKKPSFLAINPFGQVPVFLDGGLKLTESRAISEYIA 111
Cdd:cd03053   3 KLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLA 74

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 15218641  40 KIYGYPYSTNTRRVLAVLHEKGLSYDPITVNLIAGDQKKPSFLAINPFGQVPVF-LDGGLKLTESRAISEYI 110
Cdd:cd03051   2 KLYDSPTAPNPRRVRIFLAEKGIDVPLVTVDLAAGEQRSPEFLAKNPAGTVPVLeLDDGTVITESVAICRYL 73

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 15218641    39 YKIYGYPYSTNTRRVLAVLHEKGLSYDPITVNLIAGDQKKPSFLAINPFGQVPVFLDGGLKLTESRAISEYIA 111
Cdd:pfam02798   3 LTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIA 75

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15218641  40 KIYGYPYSTNTRRVLAVLHEKGLSYDPITVNLIAGDQKKPSFLAINPFGQVPVFLDGGLKLTESRAISEYI 110
Cdd:cd03042   2 ILYSYFRSSASYRVRIALNLKGLDYEYVPVNLLKGEQLSPAYRALNPQGLVPTLVIDGLVLTQSLAIIEYL 72

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15218641  39 YKIYGYPySTNTRRVLAVLHEKGLSYDPITVNLIAGDQKKPSFLAINPFGQVPVFLD---GGLKLTESRAISEYIATVH 114
Cdd:cd03048   2 ITLYTHG-TPNGFKVSIMLEELGLPYEIHPVDISKGEQKKPEFLKINPNGRIPAIVDhngTPLTVFESGAILLYLAEKY 79

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 15218641  39 YKIYGYPY--STNTRrvlAVLHEKGLSYDPITVNLIAGDQKKPSFLAINPFGQVPVF-LDGGLKLTESRAISEYIATVH 114
Cdd:cd03057   1 MKLYYSPGacSLAPH---IALEELGLPFELVRVDLRTKTQKGADYLAINPKGQVPALvLDDGEVLTESAAILQYLADLH 76

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 15218641  40 KIYGYPYSTNTRRVLAVLHEKGLSYDPITVNLIAGDQKKPSFLAINPFGQVPVFLDGGLKLTESRAISEYIA 111
Cdd:cd03045   2 DLYYLPGSPPCRAVLLTAKALGLELNLKEVNLMKGEHLKPEFLKLNPQHTVPTLVDNGFVLWESHAILIYLV 73

GST_N family, Gamma subunit of Elongation Factor 1B (EFB1gamma) subfamily; EF1Bgamma is part of the eukaryotic translation elongation factor-1 (EF1) complex which plays a central role in the elongation cycle during protein biosynthesis. EF1 consists of two functionally distinct units, EF1A and EF1B. EF1A catalyzes the GTP-dependent binding of aminoacyl-tRNA to the ribosomal A site concomitant with the hydrolysis of GTP. The resulting inactive EF1A:GDP complex is recycled to the active GTP form by the guanine-nucleotide exchange factor EF1B, a complex composed of at least two subunits, alpha and gamma. Metazoan EFB1 contain a third subunit, beta. The EF1B gamma subunit contains a GST fold consisting of an N-terminal TRX-fold domain and a C-terminal alpha helical domain. The GST-like domain of EF1Bgamma is believed to mediate the dimerization of the EF1 complex, which in yeast is a dimer of the heterotrimer EF1A:EF1Balpha:EF1Bgamma. In addition to its role in protein biosynthesis, EF1Bgamma may also display other functions. The recombinant rice protein has been shown to possess GSH conjugating activity. The yeast EF1Bgamma binds membranes in a calcium dependent manner and is also part of a complex that binds to the msrA (methionine sulfoxide reductase) promoter suggesting a function in the regulation of its gene expression.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15218641  39 YKIYGYPYSTNTRRVLAVLhekglSYDPITVNLI----AGDQKKPSFLAINPFGQVPVFL-DGGLKLTESRAISEYIA 111
Cdd:cd03044   1 GTLYTYPGNPRSLKILAAA-----KYNGLDVEIVdfqpGKENKTPEFLKKFPLGKVPAFEgADGFCLFESNAIAYYVA 73

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15218641  45 PYSTNTRRVLAvlhEKGLSYDPITVNLiagdQKKPSFLA-INPFGQVPVFLDGGLKLTESRAISEYI 110
Cdd:cd03059  10 VYSHRVRIVLA---EKGVSVEIIDVDP----DNPPEDLAeLNPYGTVPTLVDRDLVLYESRIIMEYL 69

GSH-dependent disulfide bond oxidoreductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218641   47 STNTRRVLAVLHEKGLSYDPITVNLIAGDQKKPSFLAINPFGQVPVFL-----DGG--LKLTESRAISEYIAtvhksRGT 119
Cdd:PRK13972   9 TPNGHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVdhspaDGGepLSLFESGAILLYLA-----EKT 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218641  120 QLLNYKSYKTMGTQRMWMAIESFEFDPLTSTLTWEQSIKPmyglKTDYKVVNETEAKLEKVLDIYEERLKNSSFLASNSF 199
Cdd:PRK13972  84 GLFLSHETRERAATLQWLFWQVGGLGPMLGQNHHFNHAAP----QTIPYAIERYQVETQRLYHVLNKRLENSPWLGGENY 159

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 15218641  200 TMADLYHLPNIQYLmdTHTKRMFVNRPSVRRWVAEITARPA 240
Cdd:PRK13972 160 SIADIACWPWVNAW--TRQRIDLAMYPAVKNWHERIRSRPA 198

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
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 15218641  56 VLHEKGLSYDPITVNLiaGDQKKPSFLAINPFGQVPVFLDGGLKLTESRAISEYIA 111
Cdd:cd03039  18 LLADAGVEYEDVRITY--EEWPELDLKPTLPFGQLPVLEIDGKKLTQSNAILRYLA 71

GST_N family, unknown subfamily 3; composed of uncharacterized bacterial proteins with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15218641  40 KIYGYPYSTNTRRVLAVLHEKGLS--YDPITVNLIAGDqkkPSFLAINPFGQVPV-FLDGGLKLTESRAISEYI 110
Cdd:cd03049   2 KLLYSPTSPYVRKVRVAAHETGLGddVELVLVNPWSDD---ESLLAVNPLGKIPAlVLDDGEALFDSRVICEYL 72

C-terminal, alpha helical domain of an unknown subfamily 8 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 8; composed of Agrobacterium tumefaciens GST and other uncharacterized bacterial proteins with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. The three-dimensional structure of Agrobacterium tumefaciens GST has been determined but there is no information on its functional characterization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218641 136 WMAIESFEFDPLTstltWEQSIKPMYGLKTDYKVVNETEAKLEKVLDIYEERLKNSSFLASNSFTMADLYHLPNIQYLMD 215
Cdd:cd03207   4 WLFFAAGTVEPPL----LNKALGRFFEPPWGEPAIAAAYGDLDERLAALEAALAGRPYLVGERFSAADLLLASVLRWARA 79

                        90       100
                ....*....|....*....|....*
gi 15218641 216 THtkrMFVNRPSVRRWVAEITARPA 240
Cdd:cd03207  80 FG---LLPEYPALRAYVARCTARPA 101

Glutathione S-transferase C-terminal-like, alpha helical domain of the Gamma subunit of Elongation Factor 1B and similar proteins; Glutathione S-transferase (GST) C-terminal domain family, Gamma subunit of Elongation Factor 1B (EF1Bgamma) 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 thioredoxin-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 to 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. Also included in this subfamily is the GST_C-like domain at the N-terminus of human valyl-tRNA synthetase (ValRS) and its homologs. Metazoan ValRS forms a stable complex with Elongation Factor-1H (EF-1H), and together, they catalyze consecutive steps in protein biosynthesis, tRNA aminoacylation and its transfer to EF.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218641 135 MWMAIESFEFDPLTSTLTWeqsikPMYGL-KTDYKVVNETEAKLEKVLDIYEERLKNSSFLASNSFTMADLYH----LPN 209
Cdd:cd03181   7 QWISFANSELLPAAATWVL-----PLLGIaPYNKKAVDKAKEDLKRALGVLEEHLLTRTYLVGERITLADIFVasalLRG 81

                        90       100       110
                ....*....|....*....|....*....|...
gi 15218641 210 IQYLMDTHTKRMFVNrpsVRRWVAEITARPAWK 242
Cdd:cd03181  82 FETVLDPEFRKKYPN---VTRWFNTVVNQPKFK 111

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218641  41 IYGYPYSTNTRRVLAVLHEKGLSYDPITVNLIAGDQKKPSFLAINPFGQVPVFLDGGLKLTESRAISEYI 110
Cdd:cd03052   3 LYHWTQSFSSQKVRLVIAEKGLRCEEYDVSLPLSEHNEPWFMRLNPTGEVPVLIHGDNIICDPTQIIDYL 72

stringent starvation protein A; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15218641   46 YSTNTRRVLAvlhEKGLSYDpitVNLIAGDQKKPSFLAINPFGQVPVFLDGGLKLTESRAISEYI 110
Cdd:PRK09481  21 YSHQVRIVLA---EKGVSVE---IEQVEKDNLPQDLIDLNPYQSVPTLVDRELTLYESRIIMEYL 79

C-terminal, alpha helical domain of Class Theta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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 the 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 the aryl or alkyl sulfate esters.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218641 148 TSTLTWEQSIKPMYGLKTDYKV-VNETEAKLEKVLDIYEER-LKNSSFLASNSFTMADLYHLPNIQYLMdTHTKRMFVNR 225
Cdd:cd03183  20 CAAYFWQKVLLPLFGGTPVSPEkVKKAEENLEESLDLLENKfLKDKPFLAGDEISIADLSAICEIMQPE-AAGYDVFEGR 98

                        90
                ....*....|....*.
gi 15218641 226 PSVRRWVAEITARPAW 241
Cdd:cd03183  99 PKLAAWRKRVKEAGNP 114

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15218641   169 VVNETEAKLEKVLDIYEERLKNSSFLASNSFTMADLYHLPNIQYLMDTHTKRMFVNR-PSVRRWVAE 234
Cdd:pfam13410   1 ALERAREQLRAALDALEARLADGPGLLGDRPTLADIALAPVLARLDAAYPGLDLREGyPRLRAWLER 67

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15218641 177 LEKVLDIYEERLKNSSFLASNSFTMADlyhlpnIQYLMDTHTKRMFVNR----PSVRRWVAEITARP 239
Cdd:cd03189  63 LKRHLDFLEDHLAKHPYFAGDELTAAD------IMMSFPLEAALARGPLleqyPNIAAYLERIEARP 123

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15218641 174 EAKLEkvLDIYEERLKNSSFLASNSFTMADLYHLPNIQYLM--DTHTKRMFVNRPS---VRRWVAEITARPAWKR 243
Cdd:cd10292  44 EAKRQ--LDVLDRQLATHKYLAGDEYTIADMAIWPWYGGLAlgSLYDAAEFLDVDEykhVQRWAKDIAARPAVKR 116