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 1953353893 107 YERARQKMLLELFYKI-------------------------------LGYQNTVFFGGDCISMIDYLFWPWFERLEVYGI 155
Cdd:cd03184     1 YEKAQQKMLIERFSKVpsafykflrsgedrkglkeelrsalenleeeLAKRGTPFFGGNSPGMVDYMIWPWFERLEALKL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1953353893 156 A----DCLNHTPALRLWTAAMKQDPTVCALLIDKSVFSGFLNLY 195
Cdd:cd03184    81 LdgyeLCLDRFPKLKKWMAAMKQDPAVKAFYTDPETHAEFLNSY 124

C-terminal, alpha helical domain of Class Omega Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. They contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism. Polymorphisms of the class Omega GST genes may be associated with the development of some types of cancer and the age-at-onset of both Alzheimer's and Parkinson's diseases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953353893 107 YERARQKMLLELFYKI-------------------------------LGYQNTVFFGGDCISMIDYLFWPWFERLEVYGI 155
Cdd:cd03184     1 YEKAQQKMLIERFSKVpsafykflrsgedrkglkeelrsalenleeeLAKRGTPFFGGNSPGMVDYMIWPWFERLEALKL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1953353893 156 A----DCLNHTPALRLWTAAMKQDPTVCALLIDKSVFSGFLNLY 195
Cdd:cd03184    81 LdgyeLCLDRFPKLKKWMAAMKQDPAVKAFYTDPETHAEFLNSY 124

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1953353893  30 FCPYAHRTRLVLRAKGIRHEV--ININLRNKPEWYYTKHPFGQIPVLENSKCQLIYESVIACEYLDDA 95
Cdd:pfam13409   1 FSPFSHRVRLALEEKGLPYEIelVDLDPKDKPPELLALNPLGTVPVLVLPDGTVLTDSLVILEYLEEL 68

C-terminal, alpha helical domain of Class Omega Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. They contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism. Polymorphisms of the class Omega GST genes may be associated with the development of some types of cancer and the age-at-onset of both Alzheimer's and Parkinson's diseases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953353893 107 YERARQKMLLELFYKI-------------------------------LGYQNTVFFGGDCISMIDYLFWPWFERLEVYGI 155
Cdd:cd03184     1 YEKAQQKMLIERFSKVpsafykflrsgedrkglkeelrsalenleeeLAKRGTPFFGGNSPGMVDYMIWPWFERLEALKL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1953353893 156 A----DCLNHTPALRLWTAAMKQDPTVCALLIDKSVFSGFLNLY 195
Cdd:cd03184    81 LdgyeLCLDRFPKLKKWMAAMKQDPAVKAFYTDPETHAEFLNSY 124

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1953353893  30 FCPYAHRTRLVLRAKGIRHEV--ININLRNKPEWYYTKHPFGQIPVLENSKCQLIYESVIACEYLDDA 95
Cdd:pfam13409   1 FSPFSHRVRLALEEKGLPYEIelVDLDPKDKPPELLALNPLGTVPVLVLPDGTVLTDSLVILEYLEEL 68

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1953353893  26 YSMRFCPYAHRTRLVLRAKGIRHEVININLRNKPEWYYTKHPFGQIPVLENSKcQLIYESVIACEYLDDAYPGRK 100
Cdd:pfam13417   2 YGFPGSPYARRVRIALNEKGLPYEFVPIPPGDHPPELLAKNPLGKVPVLEDDG-GILCESLAIIDYLEELYPGPP 75

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 1953353893  23 IRIYSMRFCPYAHRTRLVLRAKGIRHEVININL---RNKPEWYYTKHPFGQIPVLE-NSKCqlIYESVIACEYLDD 94
Cdd:pfam02798   3 LTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFgagPEKSPELLKLNPLGKVPALEdGGKK--LTESRAILEYIAR 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 1953353893  24 RIYSMRFCPYAHRTRLVLRAKGIRHEVININLR---NKPEWYYTKHPFGQIPVLENSKCQLIYESVIACEYLD 93
Cdd:cd03051     2 KLYDSPTAPNPRRVRIFLAEKGIDVPLVTVDLAageQRSPEFLAKNPAGTVPVLELDDGTVITESVAICRYLE 74

stringent starvation protein A; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953353893  33 YAHRTRLVLRAKGIRHEVININLRNKPEWYYTKHPFGQIPVLENSKCQLiYESVIACEYLDDAYPGRKLYPYDPYERARQ 112
Cdd:PRK09481   21 YSHQVRIVLAEKGVSVEIEQVEKDNLPQDLIDLNPYQSVPTLVDRELTL-YESRIIMEYLDERFPHPPLMPVYPVARGES 99

                  ....
gi 1953353893 113 KMLL 116
Cdd:PRK09481  100 RLMM 103

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 1953353893  32 PYAHRTRLVLRAKGIRHEVININLRNKPEWYYTKHP-FGQIPVL-ENSKCqlIYESVIACEYLDDAY 96
Cdd:cd03058    10 PFVLRVRIALALKGVPYEYVEEDLGNKSELLLASNPvHKKIPVLlHNGKP--ICESLIIVEYIDEAW 74

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1953353893  32 PYAHRTRLVLR--AKGIRHEVININLRNKPEWYYTKHPFGQIPVLENSKCQLIYESVIACEYLD 93
Cdd:cd03049    10 PYVRKVRVAAHetGLGDDVELVLVNPWSDDESLLAVNPLGKIPALVLDDGEALFDSRVICEYLD 73

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 1953353893  23 IRIYSMRFCPYAHRTRLVLRAKGIRHEVININLRN---KPEWYYTKHPFGQIPVLENSKCQLiYESVIACEYL 92
Cdd:cd03056     1 MKLYGFPLSGNCYKVRLLLALLGIPYEWVEVDILKgetRTPEFLALNPNGEVPVLELDGRVL-AESNAILVYL 72

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1953353893  23 IRIYSMRFCPYAHRTRLVLRAKGIRHEVINI 53
Cdd:COG0695     2 VTLYTTPGCPYCARAKRLLDEKGIPYEEIDV 32

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1953353893 108 ERARQKM--LLELFYKILGyqNTVFFGGDCISMIDYLFWPWFERLEVYGIADCLN-HTPALRLWTAAM 172
Cdd:cd00299    35 EAAREELpaLLAALEQLLA--GRPYLAGDQFSLADVALAPVLARLEALGPYYDLLdEYPRLKAWYDRL 100

Glutaredoxin;

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1953353893  23 IRIYSMRFCPYAHRTRLVLRAKGIRHEVINI 53
Cdd:pfam00462   1 VVLYTKPTCPFCKRAKRLLKSLGVDFEEIDV 31

C-terminal, alpha helical domain of Class Tau Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1953353893 130 FFGGDCISMID---YLFWPWFERLEVYGIADCLN--HTPALRLWTAAMKQDPTV 178
Cdd:cd03185    57 FFGGDTIGYLDialGSFLGWFKAIEEVGGVKLLDeeKFPLLAAWAERFLEREAV 110

Glutaredoxin (GRX) family; composed of GRX, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins such as ribonucleotide reductase. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH -> GSH reductase -> GSH -> GRX -> protein substrates. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress. Different classes are known including human GRX1 and GRX2, as well as E. coli GRX1 and GRX3, which are members of this family. E. coli GRX2, however, is a 24-kDa protein that belongs to the GSH S-transferase (GST) family.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1953353893  23 IRIYSMRFCPYAHRTRLVLRAKGIRHEVININ 54
Cdd:cd02066     2 VVVFSKSTCPYCKRAKRLLESLGIEFEEIDIL 33

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 1953353893  37 TRLVLRAKGIRHEVININLRNKPEW---YYTKHPFGQIPVLENSKCQLIYESVIACEYLDDAYP 97
Cdd:cd03057    14 PHIALEELGLPFELVRVDLRTKTQKgadYLAINPKGQVPALVLDDGEVLTESAAILQYLADLHP 77