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 1227955849  84 WEALEIDAIVDTLTDFRQQIANYYYDQDEATKEKKWGPLKNETVPYYMSKFDEVVKKNE-GYFVGGKLTWADIYFVGILD 162
Cdd:cd03192     1 EEEARVDAIVDTIADLRAEFAPYFYEPDGEEKKEKKKEFLEEALPKFLGKFEKILKKSGgGYFVGDKLTWADLALFDVLD 80

                          90       100
                  ....*....|....*....|....
gi 1227955849 163 YLNGMVKEDLVEKYPNLKALKEKI 186
Cdd:cd03192    81 YLLYLLPKDLLEKYPKLKALRERV 104

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 1227955849  84 WEALEIDAIVDTLTDFRQQIANYYYDQDEATKEKKWGPLKNETVPYYMSKFDEVVKKNE-GYFVGGKLTWADIYFVGILD 162
Cdd:cd03192     1 EEEARVDAIVDTIADLRAEFAPYFYEPDGEEKKEKKKEFLEEALPKFLGKFEKILKKSGgGYFVGDKLTWADLALFDVLD 80

                          90       100
                  ....*....|....*....|....
gi 1227955849 163 YLNGMVKEDLVEKYPNLKALKEKI 186
Cdd:cd03192    81 YLLYLLPKDLLEKYPKLKALRERV 104

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 1227955849   5 YKLSYFCVKALGEPIRFLLSYGGVEFEDYRFEKEQW--SQIKPTTPFGKAPVLEIDGKQTHQSAAICRYLAK 74
Cdd:cd03039     1 YKLTYFNIRGRGEPIRLLLADAGVEYEDVRITYEEWpeLDLKPTLPFGQLPVLEIDGKKLTQSNAILRYLAR 72

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1227955849  19 IRFLLSYGGVEFE----DYRFEKEQWSQIKPTTPFGKAPVLEIDGKQTHQSAAICRYLAKQFG---LNGSND---WEALE 88
Cdd:COG0625    16 VRIALEEKGLPYElvpvDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPeppLLPADPaarARVRQ 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1227955849  89 IDAIVDTLTD--FRQQIANYYYDQDEATKEKKWgplknETVPYYMSKFDEVVKKNEgYFVGGKLTWADIYFVGILDYLNG 166
Cdd:COG0625    96 WLAWADGDLHpaLRNLLERLAPEKDPAAIARAR-----AELARLLAVLEARLAGGP-YLAGDRFSIADIALAPVLRRLDR 169

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1227955849 167 MvkEDLVEKYPNLKALKEKILALPPIKAWVEKR 199
Cdd:COG0625   170 L--GLDLADYPNLAAWLARLAARPAFQRALAAA 200

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 1227955849  84 WEALEIDAIVDTLTDFRQQIANYYYDQDEATKEKKWGPLKNETVPYYMSKFDEVVKKNE-GYFVGGKLTWADIYFVGILD 162
Cdd:cd03192     1 EEEARVDAIVDTIADLRAEFAPYFYEPDGEEKKEKKKEFLEEALPKFLGKFEKILKKSGgGYFVGDKLTWADLALFDVLD 80

                          90       100
                  ....*....|....*....|....
gi 1227955849 163 YLNGMVKEDLVEKYPNLKALKEKI 186
Cdd:cd03192    81 YLLYLLPKDLLEKYPKLKALRERV 104

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 1227955849   5 YKLSYFCVKALGEPIRFLLSYGGVEFEDYRFEKEQW--SQIKPTTPFGKAPVLEIDGKQTHQSAAICRYLAK 74
Cdd:cd03039     1 YKLTYFNIRGRGEPIRLLLADAGVEYEDVRITYEEWpeLDLKPTLPFGQLPVLEIDGKKLTQSNAILRYLAR 72

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1227955849  19 IRFLLSYGGVEFE----DYRFEKEQWSQIKPTTPFGKAPVLEIDGKQTHQSAAICRYLAKQFG---LNGSND---WEALE 88
Cdd:COG0625    16 VRIALEEKGLPYElvpvDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPeppLLPADPaarARVRQ 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1227955849  89 IDAIVDTLTD--FRQQIANYYYDQDEATKEKKWgplknETVPYYMSKFDEVVKKNEgYFVGGKLTWADIYFVGILDYLNG 166
Cdd:COG0625    96 WLAWADGDLHpaLRNLLERLAPEKDPAAIARAR-----AELARLLAVLEARLAGGP-YLAGDRFSIADIALAPVLRRLDR 169

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1227955849 167 MvkEDLVEKYPNLKALKEKILALPPIKAWVEKR 199
Cdd:COG0625   170 L--GLDLADYPNLAAWLARLAARPAFQRALAAA 200

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 1227955849   5 YKLSYFCVKALGEPIRFLLSYGGVEFEDYRFEKEQWSQ--IKPTTPFGKAPVLEIDGKQTHQSAAICRYLA 73
Cdd:cd00570     1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQeeFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

C-terminal, alpha helical domain of Class Sigma Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Sigma; 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1227955849  85 EALEIDAIVDTLTDFRQQIAnyYYDQDEATKEKKWGPLKNETVPYYMSKFDEVVKKNEgYFVGGKLTWADIYFVGILDYL 164
Cdd:cd10295     3 EQCLVDALVDTLDDFMSCFP--WAEKKQDVKEKMFNEALTGPAPHLLKDLDTYLGGRE-WLVGKSVTWADFYWDTCSTTL 79

                          90       100
                  ....*....|....*....|..
gi 1227955849 165 NGMvKEDLVEKYPNLKALKEKI 186
Cdd:cd10295    80 LSF-KPDLLKNYPRLVALRDKV 100

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The class Alpha subfamily is composed of eukaryotic 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1227955849   4 KYKLSYFCVKALGEPIRFLLSYGGVEFED-YRFEKEQWSQIKP--TTPFGKAPVLEIDGKQTHQSAAICRYLAKQFGL 78
Cdd:cd03077     1 KPVLHYFNGRGRMESIRWLLAAAGVEFEEkFIESAEDLEKLKKdgSLMFQQVPMVEIDGMKLVQTRAILNYIAGKYNL 78

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 1227955849   6 KLSYFCVKALGEPIRFLLSYGGVEFEDYRFE--------KEQWSQIKPT--TPFGKAPVLEIDGKQTHQSAAICRYLAKQ 75
Cdd:cd03075     2 TLGYWDIRGLAQPIRLLLEYTGEKYEEKRYElgdapdydRSQWLNEKFKlgLDFPNLPYYIDGDVKLTQSNAILRYIARK 81

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1227955849  18 PIRFLLSY--GGVEFEDYRFEKEQWSQIKPT----TPFGKAPVLEIDGKQTHQSAAICRYLAKQFGLNGSNDW-EALEID 90
Cdd:PLN02473   14 PQRVLLCFleKGIEFEVIHVDLDKLEQKKPEhllrQPFGQVPAIEDGDLKLFESRAIARYYATKYADQGTDLLgKTLEHR 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1227955849  91 AIVDTLTDfrqqIANYYYD-------QDEATKEKKWGPLKNETVPYYMSKFDEVVKKNEG------YFVGGKLTWADI-- 155
Cdd:PLN02473   94 AIVDQWVE----VENNYFYavalplvINLVFKPRLGEPCDVALVEELKVKFDKVLDVYENrlatnrYLGGDEFTLADLth 169

                         170
                  ....*....|....*....
gi 1227955849 156 -----YFVGILDyLNGMVK 169
Cdd:PLN02473  170 mpgmrYIMNETS-LSGLVT 187

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
                  ....*....|....*....|....*....|
gi 1227955849  48 PFGKAPVLEIDGKQTHQSAAICRYLAKQFG 77
Cdd:cd03046    47 PLGKVPVLVDGDLVLTESAAIILYLAEKYG 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
                  ....*....|....*....|....*.
gi 1227955849  48 PFGKAPVLEIDGKQTHQSAAICRYLA 73
Cdd:cd03056    48 PNGEVPVLELDGRVLAESNAILVYLA 73

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 1227955849  89 IDAIVDTLTD--FRQQIANYYYDQDEATKEKKWGPLKNETVPYYMSKFDEVVKKNeGYFVGGKLTWADIYFVGILDYLNG 166
Cdd:cd00299     1 VRALEDWADAtlAPPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGR-PYLAGDQFSLADVALAPVLARLEA 79

                          90       100
                  ....*....|....*....|.
gi 1227955849 167 M-VKEDLVEKYPNLKALKEKI 186
Cdd:cd00299    80 LgPYYDLLDEYPRLKAWYDRL 100

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
                  ....*....|....*....|....*...
gi 1227955849  48 PFGKAPVLEIDGKQTHQSAAICRYLAKQ 75
Cdd:cd03053    49 PFGQIPALEDGDLKLFESRAITRYLAEK 76

C-terminal, alpha helical domain of Ure2p and related Glutathione S-transferase-like proteins; Glutathione S-transferase (GST) C-terminal domain family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p, YfcG and YghU from Escherichia coli, and related GST-like proteins. Ure2p is a regulator for nitrogen catabolism in yeast. It represses the expression of several gene products involved in the use of poor nitrogen sources when rich sources are available. A transmissible conformational change of Ure2p results in a prion called [Ure3], an inactive, self-propagating and infectious amyloid. Ure2p displays a GST fold containing an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The N-terminal thioredoxin-fold domain is sufficient to induce the [Ure3] phenotype and is also called the prion domain of Ure2p. In addition to its role in nitrogen regulation, Ure2p confers protection to cells against heavy metal ion and oxidant toxicity, and shows glutathione (GSH) peroxidase activity. YfcG and YghU are two of the nine GST homologs in the genome of Escherichia coli. They display very low or no GSH transferase, but show very good disulfide bond oxidoreductase activity. YghU also shows modest organic hydroperoxide reductase activity. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of GSH with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1227955849 125 ETVPYYMSKFDEVVKK----------NEGYFVGGKLTWADIYFVGILDYLNGMVKEDLvEKYPNLKALKEKILALPPIK 193
Cdd:cd03178    32 EKIPYAIERYTDEVKRlygvldkrlsDRPYLAGEEYSIADIALYPWTHYADLGGFADL-SEYPNVKRWLERIAARPAVQ 109

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.

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gi 1227955849  36 EKEQWSQ-IKPTTPFGKAPVLEI-DGKQTHQSAAICRYL 72
Cdd:cd03051    35 AGEQRSPeFLAKNPAGTVPVLELdDGTVITESVAICRYL 73

GST_N family, Class Omega subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. They contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism. Polymorphisms of the class Omega GST genes may be associated with the development of some types of cancer and the age-at-onset of both Alzheimer's and Parkinson's diseases.

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gi 1227955849  10 FCVKAlgEPIRFLLSYGGVEFE----------DYRFEKeqwsqikptTPFGKAPVLEID-GKQTHQSAAICRYL 72
Cdd:cd03055    26 FCPYA--QRARLVLAAKNIPHEvininlkdkpDWFLEK---------NPQGKVPALEIDeGKVVYESLIICEYL 88