Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold; The thioredoxin (TRX)-like superfamily is a large, diverse group of proteins containing a TRX fold. Many members contain a classic TRX domain with a redox active CXXC motif. They function as protein disulfide oxidoreductases (PDOs), altering the redox state of target proteins via the reversible oxidation of their active site dithiol. The PDO members of this superfamily include the families of TRX, protein disulfide isomerase (PDI), tlpA, glutaredoxin, NrdH redoxin, and bacterial Dsb proteins (DsbA, DsbC, DsbG, DsbE, DsbDgamma). Members of the superfamily that do not function as PDOs but contain a TRX-fold domain include phosducins, peroxiredoxins, glutathione (GSH) peroxidases, SCO proteins, GSH transferases (GST, N-terminal domain), arsenic reductases, TRX-like ferredoxins and calsequestrin, among others.

                         10        20
                 ....*....|....*....|....*.
gi 392934523   1 KVPAFETSDNKYIYETNAVAYYVGNS 26
Cdd:cd03044   50 KVPAFEGADGFCLFESNAIAYYVANL 75

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392934523   1 KVPAFEtSDNKYIYETNAVAYYV----GNSQLRGTSLIDQSLILQWVSFSDNEILPAACTWLFPCLGlmQYNKQSCEKAK 76
Cdd:COG0625   52 KVPVLV-DDGLVLTESLAILEYLaeryPEPPLLPADPAARARVRQWLAWADGDLHPALRNLLERLAP--EKDPAAIARAR 128

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 392934523  77 EDIKKALKVLNDHLLTRTYLVGERITQADISVFCTLLSLYQHVLEpafRAPYGNVNRWFTTLMHQPQFKAVVGE 150
Cdd:COG0625  129 AELARLLAVLEARLAGGPYLAGDRFSIADIALAPVLRRLDRLGLD---LADYPNLAAWLARLAARPAFQRALAA 199

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392934523   1 KVPAFETSDNKyIYETNAVA-YYVGNSQLRGTSLIDQSL-----ILQWVSFSDNEI----LPAACTWLF-PCLGlmqynk 69
Cdd:PLN02473  53 QVPAIEDGDLK-LFESRAIArYYATKYADQGTDLLGKTLehraiVDQWVEVENNYFyavaLPLVINLVFkPRLG------ 125

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392934523  70 QSCEKA-KEDIK----KALKVLNDHLLTRTYLVGERITQADISVFCTLLSLYQHVLEPAFRAPYGNVNRWFTTLMHQPQF 144
Cdd:PLN02473 126 EPCDVAlVEELKvkfdKVLDVYENRLATNRYLGGDEFTLADLTHMPGMRYIMNETSLSGLVTSRENLNRWWNEISARPAW 205

                 ....
gi 392934523 145 KAVV 148
Cdd:PLN02473 206 KKLM 209

Glutathione S-transferase C-terminal-like, alpha helical domain of vertebrate Valyl-tRNA synthetase; Glutathione S-transferase (GST) C-terminal domain family, Valyl-tRNA synthetase (ValRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of human ValRS and its homologs from other vertebrates such as frog and zebrafish. Aminoacyl-tRNA synthetases (aaRSs) comprise a family of enzymes that catalyze the coupling of amino acids with their matching tRNAs. This involves the formation of an aminoacyl adenylate using ATP, followed by the transfer of the activated amino acid to the 3'-adenosine moiety of the tRNA. AaRSs may also be involved in translational and transcriptional regulation, as well as in tRNA processing. They typically form large stable complexes with other proteins. 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. The GST_C-like domain of ValRS from higher eukaryotes is likely involved in protein-protein interactions, to mediate the formation of the multi-aaRS complex that acts as a molecular hub to coordinate protein synthesis. ValRSs from prokaryotes and lower eukaryotes, such as fungi and plants, do not appear to contain this GST_C-like domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392934523  36 QSLILQWVSFSDNEILPAACTWLFPCLGLMQYNKQSCEKAKEDIKKALKVLNDHLLTRTYLVGERITQADISVFCTLLSL 115
Cdd:cd10294    2 CALVWQWVSFADNELTPAACAAAFPLLGLSGSDKQNQQRSLAELQRVLKVLDCYLKLRTYLVGEAITLADIAVACALLLP 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 392934523 116 YQHVLEPAFRAPYGNVNRWFTTLMHQPQFKAVVGEIALCEKM 157
Cdd:cd10294   82 FKYVLDPARRESLLNVTRWFLTCVNQPEFLAVLGEVSLCEKA 123

Glutathione S-transferase C-terminal-like, alpha helical domain of various Aminoacyl-tRNA synthetases and similar domains; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl-tRNA synthetase (AaRS)-like subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of some eukaryotic AaRSs, as well as similar domains found in proteins involved in protein synthesis including Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 2 (AIMP2), AIMP3, and eukaryotic translation Elongation Factor 1 beta (eEF1b). AaRSs comprise a family of enzymes that catalyze the coupling of amino acids with their matching tRNAs. This involves the formation of an aminoacyl adenylate using ATP, followed by the transfer of the activated amino acid to the 3'-adenosine moiety of the tRNA. AaRSs may also be involved in translational and transcriptional regulation, as well as in tRNA processing. AaRSs in this subfamily include GluRS from lower eukaryotes, as well as GluProRS, MetRS, and CysRS from higher eukaryotes. AIMPs are non-enzymatic cofactors that play critical roles in the assembly and formation of a macromolecular multi-tRNA synthetase protein complex found in higher eukaryotes. The GST_C-like domain is involved in protein-protein interactions, mediating the formation of aaRS complexes such as the MetRS-Arc1p-GluRS ternary complex in lower eukaryotes and the multi-aaRS complex in higher eukaryotes, that act as molecular hubs for protein synthesis. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 392934523  73 EKAKEDIKKALKVLNDHLLTRTYLVGERITQADISVFCTLLSLYQhVLEPAFRAPYGNVNRWFTTLMHQ 141
Cdd:cd10289   15 LLKGKELEALLKSLNSYLASRTFLVGYSLTLADVAVFSALYPSGQ-KLSDKEKKKFPHVTRWFNHIQNL 82

Glutathione S-transferase C-terminal-like, alpha helical domain of Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 3; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein (AIMP) 3 subfamily; AIMPs are non-enzymatic cofactors that play critical roles in the assembly and formation of a macromolecular multi-tRNA synthetase protein complex that functions as a molecular hub to coordinate protein synthesis. There are three AIMPs, named AIMP1-3, which play diverse regulatory roles. AIMP3, also called p18 or eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1), contains a C-terminal domain with similarity to the C-terminal alpha helical domain of GSTs. It specifically interacts with methionyl-tRNA synthetase (MetRS) and is translocated to the nucleus during DNA synthesis or in response to DNA damage and oncogenic stress. In the nucleus, it interacts with ATM and ATR, which are upstream kinase regulators of p53. It appears to work against DNA damage in cooperation with AIMP2, and similar to AIMP2, AIMP3 is also a haploinsufficient tumor suppressor. AIMP3 transgenic mice have shorter lifespans than wild-type mice and they show characteristics of progeria, suggesting that AIMP3 may also be involved in cellular and organismal aging.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392934523  34 IDQSLILQWVSFSDNEILPAActwlfpclglmqynkqscekAKEDIKKALKVLNDHLLTRTYLVGERITQADISVFCTLL 113
Cdd:cd10305    2 EERAQVDQWLEYRVTQVAPAS--------------------DKADAKSLLKELNSYLQDRTYLVGHKLTLADVVLYYGLH 61

                         90       100       110
                 ....*....|....*....|....*....|..
gi 392934523 114 SLYQHvLEPAFRAPYGNVNRWFTTLMHQPQFK 145
Cdd:cd10305   62 PIMKD-LSPQEKEQYLNVSRWFDHVQHLPGIR 92

Glutathione S-transferase C-terminal-like, alpha helical domain of bifunctional Glutamyl-Prolyl-tRNA synthetase; Glutathione S-transferase (GST) C-terminal domain family, bifunctional GluRS-Prolyl-tRNA synthetase (GluProRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of GluProRS from higher eukaryotes. Aminoacyl-tRNA synthetases (aaRSs) comprise a family of enzymes that catalyze the coupling of amino acids with their matching tRNAs. This involves the formation of an aminoacyl adenylate using ATP, followed by the transfer of the activated amino acid to the 3'-adenosine moiety of the tRNA. AaRSs may also be involved in translational and transcriptional regulation, as well as in tRNA processing. The GST_C-like domain of GluProRS may be involved in protein-protein interactions, mediating the formation of the multi-aaRS complex in higher eukaryotes. The multi-aaRS complex acts as a molecular hub for protein synthesis. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 392934523  70 QSCEKAKEDIKKALKVLNDHLLTRTYLVGERITQADISVFCTLLSLYqhvLEPAFRAPYGNVNRWFTTLMHQ 141
Cdd:cd10309   13 AGRLSCDQDFSSALSYLDKALSLRTYLVGNSLTLADFAVWAALRGNG---EWLASKEKYVNVTRWFKFISSQ 81

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 392934523  39 ILQWVSFSDNEILPAACTWLFPCLGLMQYNKQSCEKAKEDIKKALKVLNDHLLTRTYLVGERITQADISVFCTLLSLYQH 118
Cdd:cd03207    1 YLRWLFFAAGTVEPPLLNKALGRFFEPPWGEPAIAAAYGDLDERLAALEAALAGRPYLVGERFSAADLLLASVLRWARAF 80

                         90       100
                 ....*....|....*....|....
gi 392934523 119 VLEPafraPYGNVNRWFTTLMHQP 142
Cdd:cd03207   81 GLLP----EYPALRAYVARCTARP 100

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 392934523   73 EKAKEDIKKALKVLNDHLLTRTYLVGERITQADISVFCTLLSLyqHVLEPAF--RAPYGNVNRWF 135
Cdd:pfam13410   3 ERAREQLRAALDALEARLADGPGLLGDRPTLADIALAPVLARL--DAAYPGLdlREGYPRLRAWL 65

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 392934523  73 EKAKEDIKKALKVLNDHLLTRTYLVGERITQADISVFCTLLSLyqhVLEPAFRAPYGNVNRWFTTL 138
Cdd:cd03177   37 EEKLDKLEEALEFLETFLEGSDYVAGDQLTIADLSLVATVSTL---EVVGFDLSKYPNVAAWYERL 99

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 392934523  68 NKQSCEKAKEDIKKALKVLNDHLLTRTYLVGERITQADISVFCTLLSLYQHVlePAFRAPYGNVNRWFTTLMHQPQFK 145
Cdd:cd03178   34 IPYAIERYTDEVKRLYGVLDKRLSDRPYLAGEEYSIADIALYPWTHYADLGG--FADLSEYPNVKRWLERIAARPAVQ 109

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 392934523  73 EKAKEDIKKALKVLNDHLLTRTYLVGERITQADISVFCtllSLYQHVLEPAFRAPYGNVNRWFTTLMHQPQF 144
Cdd:cd03180   42 AASLAACNKLMAILDAQLARQAYLAGDRFTLADIALGC---SVYRWLELPIERPALPHLERWYARLSQRPAF 110

C-terminal, alpha helical domain of GTT1-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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 392934523  78 DIKKALKVLNDHLLTRTYLVGERITQADIsvfctLLSLyqhVLEPAF-RAP----YGNVNRWFTTLMHQP 142
Cdd:cd03189   62 ELKRHLDFLEDHLAKHPYFAGDELTAADI-----MMSF---PLEAALaRGPlleqYPNIAAYLERIEARP 123

C-terminal, alpha helical domain of Class Theta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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 the 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 the aryl or alkyl sulfate esters.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 392934523  55 CTWLFPCLGLMQYNKQSCEKAKEDIKKALKVLNDHLL-TRTYLVGERITQADISVFCTLLSL 115
Cdd:cd03183   26 QKVLLPLFGGTPVSPEKVKKAEENLEESLDLLENKFLkDKPFLAGDEISIADLSAICEIMQP 87

C-terminal, alpha helical domain of Escherichia coli YfcG Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YfcG-like subfamily; composed of the Escherichia coli YfcG and related 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. 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. YfcG is one of nine GST homologs in Escherichia coli. It is expressed predominantly during the late stationary phase where the predominant form of GSH is glutathionylspermidine (GspSH), suggesting that YfcG might interact with GspSH. It has very low or no GSH transferase or peroxidase activity, but displays a unique disulfide bond reductase activity that is comparable to thioredoxins (TRXs) and glutaredoxins (GRXs). However, unlike TRXs and GRXs, YfcG does not contain a redox active cysteine residue and may use a bound thiol disulfide couple such as 2GSH/GSSG for activity. The crystal structure of YcfG reveals a bound GSSG molecule in its active site. The actual physiological substrates for YfcG are yet to be identified.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392934523  75 AKEDIKKALK-----------VLNDHLLTRTYLVGERITQADISVFCTLLSLYQHVLEpafRAPYGNVNRWFTTLMHQPQ 143
Cdd:cd10291   30 APEKIPYAIKrytnetkrlygVLDRRLAKSKYLAGDEYSIADIAIWPWVARHEWQGID---LADFPNLKRWFERLAARPA 106

                 ...
gi 392934523 144 FKA 146
Cdd:cd10291  107 VQK 109

C-terminal, alpha helical domain of an unknown subfamily 6 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 6; composed of uncharacterized bacterial proteins with similarity to GSTs, including Pseudomonas fluorescens GST with a known three-dimensional structure. 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. Though the three-dimensional structure of Pseudomonas fluorescens GST has been determined, there is no information on its functional characterization.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392934523  79 IKKALKVLNDHLLTRTylvGERITQADISVFCTLLSLYQHVLEPAFRAPYGNVNRWFTTLMHQPQFKA 146
Cdd:cd03205   42 IERALDALEAELGDLP---GGRLTLGDIAVACALGYLDFRFPELDWRAGHPALAAWFARFEARPSFQA 106

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
                 ....*....|....*....|....*....|....*....|
gi 392934523  73 EKAKEDIKKALKVLNDHLLTRTYLVGERITQADISVFCTL 112
Cdd:cd03190   36 DKAVKELFEALDKLEKRLSKQPYLLGDRLTEADIRLFTTL 75

Glutathione S-transferase C-terminal-like, alpha helical domain of Cysteinyl-tRNA synthetase from higher eukaryotes; Glutathione S-transferase (GST) C-terminal domain family, Cysteinyl-tRNA synthetase (CysRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of CysRS from higher eukaryotes. Aminoacyl-tRNA synthetases (aaRSs) comprise a family of enzymes that catalyze the coupling of amino acids with their matching tRNAs. This involves the formation of an aminoacyl adenylate using ATP, followed by the transfer of the activated amino acid to the 3'-adenosine moiety of the tRNA. AaRSs may also be involved in translational and transcriptional regulation, as well as in tRNA processing. The GST_C-like domain of CysRS from higher eukaryotes is likely involved in protein-protein interactions, to mediate the formation of the multi-aaRS complex that acts as a molecular hub to coordinate protein synthesis. CysRSs from prokaryotes and lower eukaryotes do not appear to contain this GST_C-like domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 392934523  86 LNDHLLTRTYLVGERITQADISVFCTLLSlyqhvlEPAfrAPYGNVNRWF 135
Cdd:cd10310   26 LNEYLSTRSYLQGFGPSQADVEVFRLLSR------PPA--DRLVHVLRWY 67

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
                 ....*....|....*....|....*....|....*....|....*....|....
gi 392934523  73 EKAKEDIKKALKVLNDHL--LTRTYLVGERITQADISVFCTLLSLYQHVLEPAF 124
Cdd:cd03192   38 EFLEEALPKFLGKFEKILkkSGGGYFVGDKLTWADLALFDVLDYLLYLLPKDLL 91