C-terminal, alpha helical domain of Class Omega-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae Omega-like subfamily; composed of three Saccharomyces cerevisiae GST omega-like (Gto) proteins, Gto1p, Gto2p (also known as Extracellular mutant protein 4 or ECM4p), and Gto3p, as well as similar uncharacterized proteins from fungi and bacteria. The three Saccharomyces cerevisiae Gto proteins are omega-class GSTs with low or no GST activity against standard substrates, but have glutaredoxin/thiol oxidoreductase and dehydroascorbate reductase activity through a single cysteine residue in the active site. Gto1p is located in the peroxisomes while Gto2p and Gto3p are cytosolic. The gene encoding Gto2p, called ECM4, is involved in cell surface biosynthesis and architecture. S. cerevisiae ECM4 mutants show increased amounts of the cell wall hexose, N-acetylglucosamine. More recently, global gene expression analysis shows that ECM4 is upregulated during genotoxic conditions and together with the expression profiles of 18 other genes could potentially differentiate between genotoxic and cytotoxic insults in yeast.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597806 161 PEPLREEIERLNGRIYPAVNNGVYRAGFATRQDAYEEAFVQLFEELDYLEGLLGERRYLAGEYLTEADIRLFTTLVRFDA 240
Cdd:cd03190   1 PEELRKEIDELNEWIYDNINNGVYKAGFATTQEAYDKAVKELFEALDKLEKRLSKQPYLLGDRLTEADIRLFTTLIRFDP 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15597806 241 VYHGHFKCNLRRIEDYPNLSGWLRELYQRPGIGETVDFEHIKGHYYASHRTINPTGIVPLGP 302
Cdd:cd03190  81 VYHQHFKCNLKTIRDYPNLWRYLRRLYQNPGVFETTNFDHIKQHYYGSHFPINPNGIVPAGP 142

glutathionine S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597806  201 QLFEELDYLEGLLGERRYLAGEYLTEADIRLFTTLVRFDAVyhghfKCNLrriEDYPNLSGWLRELYQRPGIGETVDFEH 280
Cdd:PRK10542 128 QLEKKFQYVDEALADEQWICGQRFTIADAYLFTVLRWAYAV-----KLNL---EGLEHIAAYMQRVAERPAVAAALKAEG 199

                 ..
gi 15597806  281 IK 282
Cdd:PRK10542 200 LK 201

C-terminal, alpha helical domain of Class Omega-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae Omega-like subfamily; composed of three Saccharomyces cerevisiae GST omega-like (Gto) proteins, Gto1p, Gto2p (also known as Extracellular mutant protein 4 or ECM4p), and Gto3p, as well as similar uncharacterized proteins from fungi and bacteria. The three Saccharomyces cerevisiae Gto proteins are omega-class GSTs with low or no GST activity against standard substrates, but have glutaredoxin/thiol oxidoreductase and dehydroascorbate reductase activity through a single cysteine residue in the active site. Gto1p is located in the peroxisomes while Gto2p and Gto3p are cytosolic. The gene encoding Gto2p, called ECM4, is involved in cell surface biosynthesis and architecture. S. cerevisiae ECM4 mutants show increased amounts of the cell wall hexose, N-acetylglucosamine. More recently, global gene expression analysis shows that ECM4 is upregulated during genotoxic conditions and together with the expression profiles of 18 other genes could potentially differentiate between genotoxic and cytotoxic insults in yeast.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597806 161 PEPLREEIERLNGRIYPAVNNGVYRAGFATRQDAYEEAFVQLFEELDYLEGLLGERRYLAGEYLTEADIRLFTTLVRFDA 240
Cdd:cd03190   1 PEELRKEIDELNEWIYDNINNGVYKAGFATTQEAYDKAVKELFEALDKLEKRLSKQPYLLGDRLTEADIRLFTTLIRFDP 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15597806 241 VYHGHFKCNLRRIEDYPNLSGWLRELYQRPGIGETVDFEHIKGHYYASHRTINPTGIVPLGP 302
Cdd:cd03190  81 VYHQHFKCNLKTIRDYPNLWRYLRRLYQNPGVFETTNFDHIKQHYYGSHFPINPNGIVPAGP 142

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 15597806 168 IERLNGRIYPAVNNGVYRAGFATRQDAY--EEAFVQLFEELDYLEGLLGERRYLAGEYLTEADIRLFTTLVRFDAvyhgh 245
Cdd:cd00299   5 EDWADATLAPPLVRLLYLEKVPLPKDEAavEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEA----- 79

                        90
                ....*....|....*....
gi 15597806 246 FKCNLRRIEDYPNLSGWLR 264
Cdd:cd00299  80 LGPYYDLLDEYPRLKAWYD 98

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 15597806   184 YRAGFATRQDAYEEAFVQLFEELDYLEGLLGERRYLAGEYLTEADIRLFTTLvrfdaVYHGHFKCNLRRiEDYPNLSGWL 263
Cdd:pfam00043  13 YVPPEEKKEPEVDEALEKVARVLSALEEVLKGQTYLVGDKLTLADIALAPAL-----LWLYELDPACLR-EKFPNLKAWF 86

                  ....*..
gi 15597806   264 RELYQRP 270
Cdd:pfam00043  87 ERVAARP 93

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597806    52 ACPWAHRTLIVRKLKGLEslVDVSVVSWLMRENGWTFdpahgstgdrldglaflhqrytrddPHYSGRVTVPLLWDKQAQ 131
Cdd:pfam13409   1 FSPFSHRVRLALEEKGLP--YEIELVDLDPKDKPPEL-------------------------LALNPLGTVPVLVLPDGT 53

                          90
                  ....*....|....*..
gi 15597806   132 kiVNNESADIVRIFNSA 148
Cdd:pfam13409  54 --VLTDSLVILEYLEEL 68

Glutathione S-transferase C-terminal-like, alpha helical domain of the Gamma subunit of Elongation Factor 1B and similar proteins; Glutathione S-transferase (GST) C-terminal domain family, Gamma subunit of Elongation Factor 1B (EF1Bgamma) 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 thioredoxin-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 to 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. Also included in this subfamily is the GST_C-like domain at the N-terminus of human valyl-tRNA synthetase (ValRS) and its homologs. Metazoan ValRS forms a stable complex with Elongation Factor-1H (EF-1H), and together, they catalyze consecutive steps in protein biosynthesis, tRNA aminoacylation and its transfer to EF.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597806 172 NGRIYPAVNNGVY-RAGFATR-QDAYEEAFVQLFEELDYLEGLLGERRYLAGEYLTEADIRLFTTLVRFdavYHGHFKCN 249
Cdd:cd03181  13 NSELLPAAATWVLpLLGIAPYnKKAVDKAKEDLKRALGVLEEHLLTRTYLVGERITLADIFVASALLRG---FETVLDPE 89

                        90
                ....*....|...
gi 15597806 250 LRRieDYPNLSGW 262
Cdd:cd03181  90 FRK--KYPNVTRW 100

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597806   188 FATRQDAYEEAFVQLFEE-----LDYLEGLL--GERRYLAGEYLTEADIRLFttlvrfDAVYHGHFKCNLRRIEDYPNLS 260
Cdd:pfam14497  12 YYEDEKKKAKRRKEFREErlpkfLGYFEKVLnkNGGGYLVGDKLTYADLALF------QVLDGLLYPKAPDALDKYPKLK 85

                          90
                  ....*....|..
gi 15597806   261 GWLRELYQRPGI 272
Cdd:pfam14497  86 ALHERVAARPNI 97

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 15597806 203 FEEL--DYLEGL----------LGERRYLAGEYLTEADIRLFTTLVR--------FDAvyHGHFKCNLRRIEDYPNLSGW 262
Cdd:cd03209  29 FEKLkpDYLEKLpdklklfsefLGDRPWFAGDKITYVDFLLYEALDQhrifepdcLDA--FPNLKDFLERFEALPKISAY 106

                ..
gi 15597806 263 LR 264
Cdd:cd03209 107 MK 108

C-terminal, alpha helical domain of an unknown subfamily 2 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15597806 209 LEGLLGERRYLAGEYLTEADIRLFTTLVRFDAVyhghfkcnlrRIE--DYPNLSGWLRELYQRPG 271
Cdd:cd03180  55 LDAQLARQAYLAGDRFTLADIALGCSVYRWLEL----------PIErpALPHLERWYARLSQRPA 109

glutathionine S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15597806  201 QLFEELDYLEGLLGERRYLAGEYLTEADIRLFTTLVRFDAVyhghfKCNLrriEDYPNLSGWLRELYQRPGIGETVDFEH 280
Cdd:PRK10542 128 QLEKKFQYVDEALADEQWICGQRFTIADAYLFTVLRWAYAV-----KLNL---EGLEHIAAYMQRVAERPAVAAALKAEG 199

                 ..
gi 15597806  281 IK 282
Cdd:PRK10542 200 LK 201

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.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 15597806  34 GEPAFPAEGGRYHLYVSLACPWAHRTLIVRKLKGLESLV 72
Cdd:cd03055   8 GSAEPPPVPGIIRLYSMRFCPYAQRARLVLAAKNIPHEV 46