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 17533779  85 EEEAWVDAVVDQFKDFFAEFRKLVIAKRVGKSAEELEkltaEVIKPAMDVYFKVLNGLLEKSKSGYLIGDSITFADLYIA 164
Cdd:cd03192   1 EEEARVDAIVDTIADLRAEFAPYFYEPDGEEKKEKKK----EFLEEALPKFLGKFEKILKKSGGGYFVGDKLTWADLALF 76

                        90       100
                ....*....|....*....|....*...
gi 17533779 165 DNIQTLKKYGLLEASGEQPKLAAHLEKV 192
Cdd:cd03192  77 DVLDYLLYLLPKDLLEKYPKLKALRERV 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 17533779  85 EEEAWVDAVVDQFKDFFAEFRKLVIAKRVGKSAEELEkltaEVIKPAMDVYFKVLNGLLEKSKSGYLIGDSITFADLYIA 164
Cdd:cd03192   1 EEEARVDAIVDTIADLRAEFAPYFYEPDGEEKKEKKK----EFLEEALPKFLGKFEKILKKSGGGYFVGDKLTWADLALF 76

                        90       100
                ....*....|....*....|....*...
gi 17533779 165 DNIQTLKKYGLLEASGEQPKLAAHLEKV 192
Cdd:cd03192  77 DVLDYLLYLLPKDLLEKYPKLKALRERV 104

glutathione s-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17533779    6 LSYFPVRGLAESARLLFHLAGVPFEDERVNFLDDTWEKMKG-----KTPMGQLPVLTVDDFEIPQSAAINRYLARKFGFA 80
Cdd:PTZ00057   7 LYYFDARGKAELIRLIFAYLGIEYTDKRFGENGDAFIEFKNfkkekDTPFEQVPILEMDNIIFAQSQAIVRYLSKKYKIC 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17533779   81 GKTPEEEAWVDAVVDQFKDFFAEFRKLVIAKRvgksaEELEKLTAEVikPAMDVYFKvlnGLLEKSKSGYLIGDSITFAD 160
Cdd:PTZ00057  87 GESELNEFYADMIFCGVQDIHYKFNNTNLFKQ-----NETTFLNEEL--PKWSGYFE---NILKKNHCNYFVGDNLTYAD 156

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 17533779  161 LYI---ADNIQTlkKYGllEASGEQPKLAAHLEKVYSHPNLKSYIASR 205
Cdd:PTZ00057 157 LAVfnlYDDIET--KYP--NSLKNFPLLKAHNEFISNLPNIKNYISNR 200

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 17533779     2 PSYKLSYFPVRGLAESARLLFHLAGVPFEDERVNFLD--DTWEKMKGKTPMGQLPVLTVDDFEIPQSAAINRYLAR 75
Cdd:pfam02798   1 MVLTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAgpEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

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 17533779  85 EEEAWVDAVVDQFKDFFAEFRKLVIAKRVGKSAEELEkltaEVIKPAMDVYFKVLNGLLEKSKSGYLIGDSITFADLYIA 164
Cdd:cd03192   1 EEEARVDAIVDTIADLRAEFAPYFYEPDGEEKKEKKK----EFLEEALPKFLGKFEKILKKSGGGYFVGDKLTWADLALF 76

                        90       100
                ....*....|....*....|....*...
gi 17533779 165 DNIQTLKKYGLLEASGEQPKLAAHLEKV 192
Cdd:cd03192  77 DVLDYLLYLLPKDLLEKYPKLKALRERV 104

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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 tumours.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17533779   3 SYKLSYFPVRGLAESARLLFHLAGVPFEDERVNFldDTW-EKMKGKTPMGQLPVLTVDDFEIPQSAAINRYLARK 76
Cdd:cd03076   1 PYTLTYFPVRGRAEAIRLLLADQGISWEEERVTY--EEWqESLKPKMLFGQLPCFKDGDLTLVQSNAILRHLGRK 73

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 17533779   4 YKLSYFPVRGLAESARLLFHLAGVPFEDERVNFLDDTWEKMKGKTPMGQLPVLTVDDFEIPQSAAINRYLA 74
Cdd:cd00570   1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQEEFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17533779   4 YKLSYFPVRGLAESARLLFHLAGVPFEDERVNFLddtwekmKGKT---------PMGQLPVLTVDDFEIPQSAAINRYLA 74
Cdd:cd03056   1 MKLYGFPLSGNCYKVRLLLALLGIPYEWVEVDIL-------KGETrtpeflalnPNGEVPVLELDGRVLAESNAILVYLA 73

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 17533779   5 KLSYFPVRGLAESARLLFHLAGVPFEDERV------NFLDDTW--EKMKGKTPMGQLPVLTVDDFEIPQSAAINRYLARK 76
Cdd:cd03075   2 TLGYWDIRGLAQPIRLLLEYTGEKYEEKRYelgdapDYDRSQWlnEKFKLGLDFPNLPYYIDGDVKLTQSNAILRYIARK 81

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 17533779     2 PSYKLSYFPVRGLAESARLLFHLAGVPFEDERVNFLD--DTWEKMKGKTPMGQLPVLTVDDFEIPQSAAINRYLAR 75
Cdd:pfam02798   1 MVLTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAgpEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

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 17533779   4 YKLSYFP-VRglAESARLLFHLAGVPFEDERVNFlDDTWEK---MKGKTPMGQLPVLTVDDFEIPQSAAINRYLARKFG 78
Cdd:cd03046   1 ITLYHLPrSR--SFRILWLLEELGLPYELVLYDR-GPGEQAppeYLAINPLGKVPVLVDGDLVLTESAAIILYLAEKYG 76

GST_N family, unknown subfamily 1; composed of uncharacterized proteins, predominantly from bacteria, with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17533779  20 LLFHLAGVPFEDERVNFLD-DTWEKMKGKTPMGQLPVLTVDDFEIPQSAAINRYLA 74
Cdd:cd03043  18 LLLKAAGIPFEEILVPLYTpDTRARILEFSPTGKVPVLVDGGIVVWDSLAICEYLA 73

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 17533779  86 EEAWVDAVVDQFKDFFAEFrklviakrvgKSAEELEKLTAEVIKPAMDVYFKVLNGLLEKSKSG--YLIGDSITFADLYI 163
Cdd:cd10295   3 EQCLVDALVDTLDDFMSCF----------PWAEKKQDVKEKMFNEALTGPAPHLLKDLDTYLGGreWLVGKSVTWADFYW 72

                        90       100       110
                ....*....|....*....|....*....|.
gi 17533779 164 ADNIQTLKKY--GLLeasGEQPKLAAHLEKV 192
Cdd:cd10295  73 DTCSTTLLSFkpDLL---KNYPRLVALRDKV 100

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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 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 aryl or alkyl sulfate esters.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 17533779  26 GVPFEDERVNFL--DDTWEKMKGKTPMGQLPVLTVDDFEIPQSAAINRYLARKF 77
Cdd:cd03050  23 KIPFEECPIDLRkgEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

GST_N family, Metaxin subfamily; composed of metaxins and related proteins. Metaxin 1 is a component of a preprotein import complex of the mitochondrial outer membrane. It extends to the cytosol and is anchored to the mitochondrial membrane through its C-terminal domain. In mice, metaxin is required for embryonic development. In humans, alterations in the metaxin gene may be associated with Gaucher disease. Metaxin 2 binds to metaxin 1 and may also play a role in protein translocation into the mitochondria. Genome sequencing shows that a third metaxin gene also exists in zebrafish, Xenopus, chicken and mammals. Sequence analysis suggests that all three metaxins share a common ancestry and that they possess similarity to GSTs. Also included in the subfamily are uncharacterized proteins with similarity to metaxins, including a novel GST from Rhodococcus with toluene o-monooxygenase and glutamylcysteine synthetase activities.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17533779  21 LFHLAGVPFEderVNFLDDTWekmkgKTPMGQLPVLTVDDFEIPQSAAINRYLARK 76
Cdd:cd03054  25 YLRMAGIPYE---VVFSSNPW-----RSPTGKLPFLELNGEKIADSEKIIEYLKKK 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
                ....*....|....*....|....*....|....*....|....*..
gi 17533779 150 YLIGDSITFADLYIADNIQTLKKYGLLEASgeqPKLAAHLEKVYSHP 196
Cdd:cd03207  57 YLVGERFSAADLLLASVLRWARAFGLLPEY---PALRAYVARCTARP 100

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17533779 136 FKVLNGLLEKS-KSGYLIGDSITFAD---LYIADNIQTLKKyGLLEASgeqPKLAAHLEKVYSHPNLKSYIASR 205
Cdd:cd03210  44 LKPFEKLLAKNnGKGFIVGDKISFADynlFDLLDIHLVLAP-GCLDAF---PLLKAFVERLSARPKLKAYLESD 113

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 17533779  90 VDAVVDQF-KDFFAEFRKLVIAKRVGKSAEELEKltaEVIKPAMDVYFKVLNGLLEKSksGYLIGDSITFADLYIADNIQ 168
Cdd:cd00299   1 VRALEDWAdATLAPPLVRLLYLEKVPLPKDEAAV---EAAREELPALLAALEQLLAGR--PYLAGDQFSLADVALAPVLA 75

                        90       100
                ....*....|....*....|....*
gi 17533779 169 TLKKYGLLEASGEQ-PKLAAHLEKV 192
Cdd:cd00299  76 RLEALGPYYDLLDEyPRLKAWYDRL 100