C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Alpha subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal 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 Alpha subfamily is composed of vertebrate GSTs which can form homodimer and heterodimers. There are at least six types of class Alpha GST subunits in rats, four of which have human counterparts, resulting in many possible isoenzymes with different activities, tissue distribution and substrate specificities. Human GSTA1-1 and GSTA2-2 show high GSH peroxidase activity. GSTA3-3 catalyzes the isomerization of intermediates in steroid hormone biosynthesis. GSTA4-4 preferentially catalyzes the GSH conjugation of alkenals.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978038  86 LKERAWIDMYVEGTTDLMGMIMYLPFQAADTKEKNLALIIERATTRYFPVYEKALKDHGQDYLVGNKLSWADIHLLEAIL 165
Cdd:cd03208     1 LKERALIDMYVEGTADLMEMIMMLPFLPPEEKEAKLALIKEKAKNRYFPVFEKVLKDHGQDFLVGNKLSRADVQLLEAIL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1728978038 166 MAEECKPDILSAFPLLQAFKGRTSNIPTIKKFLQPGSQRKPPTDEKAVAMVKKIY 220
Cdd:cd03208    81 MVEELDPSILSDFPLLQAFKTRISNIPTIKKFLQPGSKRKPPPDEKYVETVRKVF 135

C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Alpha subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal 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 Alpha subfamily is composed of vertebrate GSTs which can form homodimer and heterodimers. There are at least six types of class Alpha GST subunits in rats, four of which have human counterparts, resulting in many possible isoenzymes with different activities, tissue distribution and substrate specificities. Human GSTA1-1 and GSTA2-2 show high GSH peroxidase activity. GSTA3-3 catalyzes the isomerization of intermediates in steroid hormone biosynthesis. GSTA4-4 preferentially catalyzes the GSH conjugation of alkenals.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978038  86 LKERAWIDMYVEGTTDLMGMIMYLPFQAADTKEKNLALIIERATTRYFPVYEKALKDHGQDYLVGNKLSWADIHLLEAIL 165
Cdd:cd03208     1 LKERALIDMYVEGTADLMEMIMMLPFLPPEEKEAKLALIKEKAKNRYFPVFEKVLKDHGQDFLVGNKLSRADVQLLEAIL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1728978038 166 MAEECKPDILSAFPLLQAFKGRTSNIPTIKKFLQPGSQRKPPTDEKAVAMVKKIY 220
Cdd:cd03208    81 MVEELDPSILSDFPLLQAFKTRISNIPTIKKFLQPGSKRKPPPDEKYVETVRKVF 135

glutathione s-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978038   1 MAGKPKLHYSNGRGRMESIRWLLATAGVEFEEQFIEKKED----LEKLRNDGYLLFQQVPMVEIDGMKMVQTRAIGSYIA 76
Cdd:PTZ00057    1 MAEEIVLYYFDARGKAELIRLIFAYLGIEYTDKRFGENGDafieFKNFKKEKDTPFEQVPILEMDNIIFAQSQAIVRYLS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978038  77 AKYNLYGKDLKERAWIDMYVEGTTDLmgmimYLPFQAADTKEKNLALIIERATTRYFPVYEKALKDHGQDYLVGNKLSWA 156
Cdd:PTZ00057   81 KKYKICGESELNEFYADMIFCGVQDI-----HYKFNNTNLFKQNETTFLNEELPKWSGYFENILKKNHCNYFVGDNLTYA 155

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1728978038 157 DIHLLEAILMAEECKPDILSAFPLLQAFKGRTSNIPTIKKFL 198
Cdd:PTZ00057  156 DLAVFNLYDDIETKYPNSLKNFPLLKAHNEFISNLPNIKNYI 197

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978038   6 KLHYSNGRGRMESIRWLLATAGVEFEEQFIekkeDLEK--LRNDGYLL---FQQVPMVEIDGMKMVQTRAIGSYIAAKY- 79
Cdd:COG0625     3 KLYGSPPSPNSRRVRIALEEKGLPYELVPV----DLAKgeQKSPEFLAlnpLGKVPVLVDDGLVLTESLAILEYLAERYp 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978038  80 --NLYGKDLKERAWIDMYV-EGTTDLMGMIMYLPFQAADTKEKNLALIIERATTRYFPVYEKALKDHgqDYLVGNKLSWA 156
Cdd:COG0625    79 epPLLPADPAARARVRQWLaWADGDLHPALRNLLERLAPEKDPAAIARARAELARLLAVLEARLAGG--PYLAGDRFSIA 156

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 1728978038 157 DIHLLEAILMAEECKPDiLSAFPLLQAFKGRTSNIPTIKKFLQPG 201
Cdd:COG0625   157 DIALAPVLRRLDRLGLD-LADYPNLAAWLARLAARPAFQRALAAA 200

C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Alpha subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal 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 Alpha subfamily is composed of vertebrate GSTs which can form homodimer and heterodimers. There are at least six types of class Alpha GST subunits in rats, four of which have human counterparts, resulting in many possible isoenzymes with different activities, tissue distribution and substrate specificities. Human GSTA1-1 and GSTA2-2 show high GSH peroxidase activity. GSTA3-3 catalyzes the isomerization of intermediates in steroid hormone biosynthesis. GSTA4-4 preferentially catalyzes the GSH conjugation of alkenals.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978038  86 LKERAWIDMYVEGTTDLMGMIMYLPFQAADTKEKNLALIIERATTRYFPVYEKALKDHGQDYLVGNKLSWADIHLLEAIL 165
Cdd:cd03208     1 LKERALIDMYVEGTADLMEMIMMLPFLPPEEKEAKLALIKEKAKNRYFPVFEKVLKDHGQDFLVGNKLSRADVQLLEAIL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1728978038 166 MAEECKPDILSAFPLLQAFKGRTSNIPTIKKFLQPGSQRKPPTDEKAVAMVKKIY 220
Cdd:cd03208    81 MVEELDPSILSDFPLLQAFKTRISNIPTIKKFLQPGSKRKPPPDEKYVETVRKVF 135

GST_N family, Class Sigma_like; composed of GSTs belonging to class Sigma and similar proteins, including GSTs from class Mu, Pi and Alpha. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Vertebrate class Sigma GSTs are characterized as GSH-dependent hematopoietic prostaglandin (PG) D synthases and are responsible for the production of PGD2 by catalyzing the isomerization of PGH2. The functions of PGD2 include the maintenance of body temperature, inhibition of platelet aggregation, bronchoconstriction, vasodilation and mediation of allergy and inflammation. Other class Sigma members include the class II insect GSTs, S-crystallins from cephalopods and 28-kDa GSTs from parasitic flatworms. Drosophila GST2 is associated with indirect flight muscle and exhibits preference for catalyzing GSH conjugation to lipid peroxidation products, indicating an anti-oxidant role. S-crystallin constitutes the major lens protein in cephalopod eyes and is responsible for lens transparency and proper refractive index. The 28-kDa GST from Schistosoma is a multifunctional enzyme, exhibiting GSH transferase, GSH peroxidase and PGD2 synthase activities, and may play an important role in host-parasite interactions. Also members are novel GSTs from the fungus Cunninghamella elegans, designated as class Gamma, and from the protozoan Blepharisma japonicum, described as a light-inducible GST.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1728978038   5 PKLHYSNGRGRMESIRWLLATAGVEFEEQFIEKKEDlEKLRNDGYLLFQQVPMVEIDGMKMVQTRAIGSYIA 76
Cdd:cd03039     1 YKLTYFNIRGRGEPIRLLLADAGVEYEDVRITYEEW-PELDLKPTLPFGQLPVLEIDGKKLTQSNAILRYLA 71

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978038 101 DLMGMIMYLPFQAADTKEKNL-ALIIERATTRYFPVYEKALKDHGQDYLVGNKLSWADIHLLEAILMAEE-CKPDILSAF 178
Cdd:pfam14497   2 DLHHPIASSLYYEDEKKKAKRrKEFREERLPKFLGYFEKVLNKNGGGYLVGDKLTYADLALFQVLDGLLYpKAPDALDKY 81

                          90       100
                  ....*....|....*....|.
gi 1728978038 179 PLLQAFKGRTSNIPTIKKFLQ 199
Cdd:pfam14497  82 PKLKALHERVAARPNIKAYLA 102

C-terminal, alpha helical domain of Class Sigma-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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-like members include the class II insect GSTs, S-crystallins from cephalopods, nematode-specific GSTs, 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. Members also include novel GSTs from the fungus Cunninghamella elegans, designated as class Gamma, and from the protozoan Blepharisma japonicum, described as a light-inducible GST.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978038  88 ERAWIDMYVEGTTDLMGMIMYLPF--QAADTKEKNLALIIERATtRYFPVYEKALKDHGQDYLVGNKLSWADIHLLEAIL 165
Cdd:cd03192     2 EEARVDAIVDTIADLRAEFAPYFYepDGEEKKEKKKEFLEEALP-KFLGKFEKILKKSGGGYFVGDKLTWADLALFDVLD 80

                          90       100
                  ....*....|....*....|...
gi 1728978038 166 MAEECKP-DILSAFPLLQAFKGR 187
Cdd:cd03192    81 YLLYLLPkDLLEKYPKLKALRER 103

C-terminal, alpha helical domain of Class Pi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Pi subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal 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 Pi GST is a homodimeric eukaryotic protein. The human GSTP1 is mainly found in erythrocytes, kidney, placenta and fetal liver. It is involved in stress responses and in cellular proliferation pathways as an inhibitor of JNK (c-Jun N-terminal kinase). Following oxidative stress, monomeric GSTP1 dissociates from JNK and dimerizes, losing its ability to bind JNK and causing an increase in JNK activity, thereby promoting apoptosis. GSTP1 is expressed in various tumors and is the predominant GST in a wide range of cancer cells. It has been implicated in the development of multidrug-resistant tumors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978038  87 KERAWIDMYVEGTTDLMGMIMYLPFQAADT-KEKNLALIIERattryFPVYEKALKDH-GQDYLVGNKLSWADIHLLEAI 164
Cdd:cd03210     2 KEAALIDMVNDGVEDLRLKYVRMIYQNYEAgKDDYIKDLPEQ-----LKPFEKLLAKNnGKGFIVGDKISFADYNLFDLL 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1728978038 165 LMAEECKPDILSAFPLLQAFKGRTSNIPTIKKFLQPGSQRKPP 207
Cdd:cd03210    77 DIHLVLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNRP 119

Glutathione S-transferase (GST) family, N-terminal domain; a large, diverse group of cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. In addition, GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. This family, also referred to as soluble GSTs, is the largest family of GSH transferases and is only distantly related to the mitochondrial GSTs (GSTK subfamily, a member of the DsbA family). Soluble GSTs bear no structural similarity to microsomal GSTs (MAPEG family) and display additional activities unique to their group, such as catalyzing thiolysis, reduction and isomerization of certain compounds. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Based on sequence similarity, different classes of GSTs have been identified, which display varying tissue distribution, substrate specificities and additional specific activities. In humans, GSTs display polymorphisms which may influence individual susceptibility to diseases such as cancer, arthritis, allergy and sclerosis. Some GST family members with non-GST functions include glutaredoxin 2, the CLIC subfamily of anion channels, prion protein Ure2p, crystallins, metaxin 2 and stringent starvation protein A.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1728978038   5 PKLHYSNGRGRMESIRWLLATAGVEFEEQFIekkeDLEKLRNDGYLL---FQQVPMVEIDGMKMVQTRAIGSYIA 76
Cdd:cd00570     1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPV----DLGEGEQEEFLAlnpLGKVPVLEDGGLVLTESLAILEYLA 71

C-terminal, alpha helical domain of Class Mu Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Mu 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 class Mu subfamily is composed of eukaryotic GSTs. In rats, at least six distinct class Mu subunits have been identified, with homologous genes in humans for five of these subunits. Class Mu GSTs can form homodimers and heterodimers, giving a large number of possible isoenzymes that can be formed, all with overlapping activities but different substrate specificities. They are the most abundant GSTs in human liver, skeletal muscle and brain, and are believed to provide protection against diseases including cancer and neurodegenerative disorders. Some isoenzymes have additional specific functions. Human GST M1-1 acts as an endogenous inhibitor of ASK1 (apoptosis signal-regulating kinase 1) thereby suppressing ASK1-mediated cell death. Human GSTM2-2 and 3-3 have been identified as prostaglandin E2 synthases in the brain and may play crucial roles in temperature and sleep-wake regulation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978038  87 KERAWIDMYVEGTTDLM---GMIMYLP-FQAAdtKEKNLALIIERattryFPVYEKALKDHgqDYLVGNKLSWADIHLLE 162
Cdd:cd03209     1 KERIRVDMLEQQAMDLRmglIRICYSPdFEKL--KPDYLEKLPDK-----LKLFSEFLGDR--PWFAGDKITYVDFLLYE 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1728978038 163 AILMAEECKPDILSAFPLLQAFKGRTSNIPTIKKFLQpgSQR 204
Cdd:cd03209    72 ALDQHRIFEPDCLDAFPNLKDFLERFEALPKISAYMK--SDR 111

GST_N family, Class Mu subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The class Mu subfamily is composed of eukaryotic GSTs. In rats, at least six distinct class Mu subunits have been identified, with homologous genes in humans for five of these subunits. Class Mu GSTs can form homodimers and heterodimers, giving a large number of possible isoenzymes that can be formed, all with overlapping activities but different substrate specificities. They are the most abundant GSTs in human liver, skeletal muscle and brain, and are believed to provide protection against diseases including cancer and neurodegenerative disorders. Some isoenzymes have additional specific functions. Human GST M1-1 acts as an endogenous inhibitor of ASK1 (apoptosis signal-regulating kinase 1), thereby suppressing ASK1-mediated cell death. Human GSTM2-2 and 3-3 have been identified as prostaglandin E2 synthases in the brain and may play crucial roles in temperature and sleep-wake regulation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978038   5 PKLHYSNGRGRMESIRWLLATAGVEFEEQFIEKKE----DLEKLRNDGYLL---FQQVPMVEIDGMKMVQTRAIGSYIAA 77
Cdd:cd03075     1 PTLGYWDIRGLAQPIRLLLEYTGEKYEEKRYELGDapdyDRSQWLNEKFKLgldFPNLPYYIDGDVKLTQSNAILRYIAR 80

                  ..
gi 1728978038  78 KY 79
Cdd:cd03075    81 KH 82

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1728978038   5 PKLHYSNgRGRMESIRWLLATAGVEFEeqFIEKKEDLEKLRNDGYLLFQ---QVPMVEIDGMKMVQTRAIGSYIAAKY 79
Cdd:cd03046     1 ITLYHLP-RSRSFRILWLLEELGLPYE--LVLYDRGPGEQAPPEYLAINplgKVPVLVDGDLVLTESAAIILYLAEKY 75

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1728978038 130 TRYFPVYEKALKDHGqdYLVGNKLSWADIHLLEAILMAEECKPDiLSAFPLLQAFKGRTSNIP 192
Cdd:cd03189    64 KRHLDFLEDHLAKHP--YFAGDELTAADIMMSFPLEAALARGPL-LEQYPNIAAYLERIEARP 123

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1728978038 125 IERATT---RYFPVYEKALKDHgqDYLVGNKLSWADIHLLEAILMAEECKPDILSAFPLLQAFKGRTSNIPTIKK 196
Cdd:cd03178    38 IERYTDevkRLYGVLDKRLSDR--PYLAGEEYSIADIALYPWTHYADLGGFADLSEYPNVKRWLERIAARPAVQK 110