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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 148699935   25 PQEKVERNRDRMVLVLQQLEDKfLRDRAFLVGQQVTLADLMSLEELMQPVALGYN-LFEGRPQLTAWRERVEA 96
Cdd:pfam00043  20 KEPEVDEALEKVARVLSALEEV-LKGQTYLVGDKLTLADIALAPALLWLYELDPAcLREKFPNLKAWFERVAA 91

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148699935   8 VPWIYSKVLGPLIGVQVPQEKVERNRDRMVLVLQQLEdKFLRDRAFLVGQQVTLADLM--SLEELMQPVALGYNLFEGRP 85
Cdd:cd00299   13 APPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALE-QLLAGRPYLAGDQFSLADVAlaPVLARLEALGPYYDLLDEYP 91

                 ....*....
gi 148699935  86 QLTAWRERV 94
Cdd:cd00299   92 RLKAWYDRL 100

C-terminal, alpha helical domain of Class Delta and Epsilon Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Delta and Epsilon 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. 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 class Delta and Epsilon subfamily is made up primarily of insect GSTs, which play major roles in insecticide resistance by facilitating reductive dehydrochlorination of insecticides or conjugating them with GSH to produce water-soluble metabolites that are easily excreted. They are also implicated in protection against cellular damage by oxidative stress.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148699935  12 YSKVLGPLI--GVQVPQEKVERnrdrmvlVLQQLE--DKFLRDRAFLVGQQVTLADLMSLEELMQPVALGYNLfEGRPQL 87
Cdd:cd03177   21 LRDYYYPILfgGAEPPEEKLDK-------LEEALEflETFLEGSDYVAGDQLTIADLSLVATVSTLEVVGFDL-SKYPNV 92

                         90       100
                 ....*....|....*....|.
gi 148699935  88 TAWRERVEAFL-GAELCQEAH 107
Cdd:cd03177   93 AAWYERLKALPpGEEENGEGA 113

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.

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gi 148699935   9 PWIYskvlgPLIGV-QVPQEKVERNRDRMVLVLQQLEdKFLRDRAFLVGQQVTLADLM 65
Cdd:cd03181   22 TWVL-----PLLGIaPYNKKAVDKAKEDLKRALGVLE-EHLLTRTYLVGERITLADIF 73

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.

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gi 148699935  14 KVLGPLIGVQVPQEKVERNRDRMVLVLQQLEDKfLRDRAFLVGQQVTLADLMSLEELMQPVALGynLFEGRPQLTAWRER 93
Cdd:cd03207   19 KALGRFFEPPWGEPAIAAAYGDLDERLAALEAA-LAGRPYLVGERFSAADLLLASVLRWARAFG--LLPEYPALRAYVAR 95

                 ...
gi 148699935  94 VEA 96
Cdd:cd03207   96 CTA 98

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 148699935  27 EKVERNRDRMV----LVLQQLEdKFL--RDRAFLVGQQVTLADLMSLEELMQP-VALGYNLFEGRPQLTAWRERV 94
Cdd:cd03192   31 EKKEKKKEFLEealpKFLGKFE-KILkkSGGGYFVGDKLTWADLALFDVLDYLlYLLPKDLLEKYPKLKALRERV 104

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 148699935   29 VERNRDRMVLVLQQLEdKFLRDRAFLVGQQVTLADLM--SLEELMQPVALGYNLFEGRPQLTAWRER 93
Cdd:pfam13410   2 LERAREQLRAALDALE-ARLADGPGLLGDRPTLADIAlaPVLARLDAAYPGLDLREGYPRLRAWLER 67