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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196501967  97 AISWMFAALNTVEPPVFDHSLARILERdqPWYEQRLRALEESIRKRLDSLSARLGDADWLDGA-FSAGDLLMVTVLLRLK 175
Cdd:cd03207     1 YLRWLFFAAGTVEPPLLNKALGRFFEP--PWGEPAIAAAYGDLDERLAALEAALAGRPYLVGErFSAADLLLASVLRWAR 78

                          90       100
                  ....*....|....*....|...
gi 1196501967 176 SSNILDEYPNLAAYVARAEARPA 198
Cdd:cd03207    79 AFGLLPEYPALRAYVARCTARPA 101

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196501967  47 EPAHLALQPFGQIPTYEEGDLTLFESGAIVLHIAERHGG----LLPDETNARARAISWMFAALNTVEPPVFDHSLARILE 122
Cdd:PLN02395   41 QPEYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKYRSqgpdLLGKTIEERGQVEQWLDVEATSYHPPLLNLTLHILFA 120

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196501967 123 RDQ--PWYEQRLRALEESIRKRLDSLSARLGDADWLDGAF-SAGDL--LMVTVLLR--LKSSNILDEYPNLAAYVARAEA 195
Cdd:PLN02395  121 SKMgfPADEKVIKESEEKLAKVLDVYEARLSKSKYLAGDFvSLADLahLPFTEYLVgpIGKAYLIKDRKHVSAWWDDISS 200

                  ....*....
gi 1196501967 196 RPAYQRAFA 204
Cdd:PLN02395  201 RPAWKEVLA 209

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196501967  97 AISWMFAALNTVEPPVFDHSLARILERdqPWYEQRLRALEESIRKRLDSLSARLGDADWLDGA-FSAGDLLMVTVLLRLK 175
Cdd:cd03207     1 YLRWLFFAAGTVEPPLLNKALGRFFEP--PWGEPAIAAAYGDLDERLAALEAALAGRPYLVGErFSAADLLLASVLRWAR 78

                          90       100
                  ....*....|....*....|...
gi 1196501967 176 SSNILDEYPNLAAYVARAEARPA 198
Cdd:cd03207    79 AFGLLPEYPALRAYVARCTARPA 101

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 1196501967   3 ITITAFERSPdrgrglaRDMRVRWALEEVGQPYEVRLVSFKAMTEPAHLALQPFGQIPTYEEGDLTLFESGAIVLHIA 80
Cdd:cd00570     1 LKLYYFPGSP-------RSLRVRLALEEKGLPYELVPVDLGEGEQEEFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1196501967  15 GRGLARDMRVRWALEEVGQPYEVRLVSFKAMTE--PAHLALQPFGQIPTYEEGDLTLFESGAIVLHIAE 81
Cdd:pfam02798   8 IRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEksPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

GST_N family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p and related GSTs. Ure2p is a regulator for nitrogen catabolism in yeast. It represses the expression of several gene products involved in the use of poor nitrogen sources when rich sources are available. A transmissible conformational change of Ure2p results in a prion called [Ure3], an inactive, self-propagating and infectious amyloid. Ure2p displays a GST fold containing an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The N-terminal TRX-fold domain is sufficient to induce the [Ure3] phenotype and is also called the prion domain of Ure2p. In addition to its role in nitrogen regulation, Ure2p confers protection to cells against heavy metal ion and oxidant toxicity, and shows glutathione (GSH) peroxidase activity. Characterized GSTs in this subfamily include Aspergillus fumigatus GSTs 1 and 2, and Schizosaccharomyces pombe GST-I. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of GSH with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1196501967  27 ALEEVGQPYEVRLVSFKAMT--EPAHLALQPFGQIPT---YEEGDLTLFESGAIVLHIAERHG 84
Cdd:cd03048    18 MLEELGLPYEIHPVDISKGEqkKPEFLKINPNGRIPAivdHNGTPLTVFESGAILLYLAEKYD 80

GST_N family, unknown subfamily 2; 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. The sequence from Burkholderia cepacia was identified as part of a gene cluster involved in the degradation of 2,4,5-trichlorophenoxyacetic acid. Some GSTs (e.g. Class Zeta and Delta) are known to catalyze dechlorination reactions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196501967  23 RVRWALEEVGQPYEVRLV--SFKAMTEPAHLALQPFGQIPTYEEGDLTLFESGAIVLHIA 80
Cdd:cd03047    14 KVLWLLDELGLPYERIDAggQFGGLDTPEFLAMNPNGRVPVLEDGDFVLWESNAILRYLA 73

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1196501967  22 MRVRWALEEVGQPYEVRLVSfKAMTEPAHLALQPFGQIPTYEEGDLTLFESGAIVLHIAERHGG 85
Cdd:pfam13417  11 RRVRIALNEKGLPYEFVPIP-PGDHPPELLAKNPLGKVPVLEDDGGILCESLAIIDYLEELYPG 73

GSH-dependent disulfide bond oxidoreductase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196501967  28 LEEVGQPYEVRLVSFK--AMTEPAHLALQPFGQIPT---YEEGD----LTLFESGAIVLHIAERHGGLLPDETNARARAI 98
Cdd:PRK13972   19 LEEAELDYRLIKVDLGkgGQFRPEFLRISPNNKIPAivdHSPADggepLSLFESGAILLYLAEKTGLFLSHETRERAATL 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196501967  99 SWMFAALNTVEPPV-----FDHSLARILERDQPWYEQRLRALEESIRKRLDslsarlgDADWLDGA-FSAGDLLMVTVLL 172
Cdd:PRK13972   99 QWLFWQVGGLGPMLgqnhhFNHAAPQTIPYAIERYQVETQRLYHVLNKRLE-------NSPWLGGEnYSIADIACWPWVN 171

                         170       180
                  ....*....|....*....|....*..
gi 1196501967 173 RLKSSNI-LDEYPNLAAYVARAEARPA 198
Cdd:PRK13972  172 AWTRQRIdLAMYPAVKNWHERIRSRPA 198

GST_N family, Stringent starvation protein A (SspA) subfamily; SspA is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation. SspA adopts the GST fold with an N-terminal TRX-fold domain and a C-terminal alpha helical domain, but it does not bind glutathione (GSH) and lacks GST activity. SspA is highly conserved among gram-negative bacteria. Related proteins found in Neisseria (called RegF), Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1196501967  23 RVRWALEEVGQPYEVRLVsfKAMTEPAHLA-LQPFGQIPTYEEGDLTLFESGAIVLHIAER 82
Cdd:cd03059    14 RVRIVLAEKGVSVEIIDV--DPDNPPEDLAeLNPYGTVPTLVDRDLVLYESRIIMEYLDER 72

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196501967  19 ARDMRVRWALEEVGQPYEVRLVSFKAMTE--PAHLALQPFGQIPTYEEGDLTLFESGAIVLHIAERHG----GLLPDETN 92
Cdd:PLN02473   12 ANPQRVLLCFLEKGIEFEVIHVDLDKLEQkkPEHLLRQPFGQVPAIEDGDLKLFESRAIARYYATKYAdqgtDLLGKTLE 91

                  ....*...
gi 1196501967  93 ARARAISW 100
Cdd:PLN02473   92 HRAIVDQW 99

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 1196501967  12 PDRGRGLArdmrVRWALEEVGQPYE-VRLVSFKAMTEPAHLALqPFGQIPTYEEGDLTLFESGAIVLHIA 80
Cdd:cd03039     7 NIRGRGEP----IRLLLADAGVEYEdVRITYEEWPELDLKPTL-PFGQLPVLEIDGKKLTQSNAILRYLA 71

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1196501967  36 EVRLVSFKAMTE---PAHLALQPFGQIPTYE-EGDLTLFESGAIVLHIAE 81
Cdd:cd03044    25 DVEIVDFQPGKEnktPEFLKKFPLGKVPAFEgADGFCLFESNAIAYYVAN 74

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1196501967  24 VRWALEEVGQPYEVRLVSFKAM--TEPAHLALQPFGQIPTYEEGDLTLFESGAIVLHIAERH 83
Cdd:cd03050    15 VYIFLKLNKIPFEECPIDLRKGeqLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

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 1196501967 100 WMFAALNTVEPPVFDHSLARilERDQPWYEQRLRALEESIRKRLDSLSARLGDADWLDG-AFSAGDLLMVTVLLRLK--- 175
Cdd:cd00299     4 LEDWADATLAPPLVRLLYLE--KVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGdQFSLADVALAPVLARLEalg 81

                          90
                  ....*....|....*...
gi 1196501967 176 -SSNILDEYPNLAAYVAR 192
Cdd:cd00299    82 pYYDLLDEYPRLKAWYDR 99

Glutathione S-transferase, C-terminal domain; GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins in E. coli are also included in the alignment but are not known to have GST activity. The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain. In plants, GSTs are encoded by a large gene family (48 GST genes in Arabidopsis) and can be divided into the phi, tau, theta, zeta, and lambda classes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196501967 122 ERDQPWYEqrlrALEESIRKRLDSLSARLGDADWL-DGAFSAGDLLMVTVLL---RLKSSNILDEYPNLAAYVARAEARP 197
Cdd:pfam00043  18 EKKEPEVD----EALEKVARVLSALEEVLKGQTYLvGDKLTLADIALAPALLwlyELDPACLREKFPNLKAWFERVAARP 93

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 1196501967 125 QPWYEQRLRALEESIRKRLDSLSARLGDADWLDGA-FSAGDLLMVTVLLRLK--SSNILDEYPNLAAYVARAEARP---A 198
Cdd:cd03209    26 SPDFEKLKPDYLEKLPDKLKLFSEFLGDRPWFAGDkITYVDFLLYEALDQHRifEPDCLDAFPNLKDFLERFEALPkisA 105

                  .
gi 1196501967 199 Y 199
Cdd:cd03209   106 Y 106

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196501967  93 ARARAISWMFAALNTVEP--PVFDHSLaRILERDQPWYEQRLRALEESIRKRLDslsARLGDADWLDGA-FSAGDLLMV- 168
Cdd:cd03178     1 ERAEVLQWLFFQMSGLGPmfGQAGHFL-YFAPEKIPYAIERYTDEVKRLYGVLD---KRLSDRPYLAGEeYSIADIALYp 76

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1196501967 169 -TVLLRLKSSNILDEYPNLAAYVARAEARPAYQR 201
Cdd:cd03178    77 wTHYADLGGFADLSEYPNVKRWLERIAARPAVQK 110