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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715  91 ARAQVHEYLGWHADNIRGTFGVLLWTKVLGPLIGVQ-VPQEKVERNRDRMVLVLQQLEDKFLRDRAFLVGQQVTLADLMS 169
Cdd:cd03183    1 KRARVDEYLAWQHTNLRLGCAAYFWQKVLLPLFGGTpVSPEKVKKAEENLEESLDLLENKFLKDKPFLAGDEISIADLSA 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 568966715 170 LEELMQPVALGYNLFEGRPQLTAWRERVEAFlGAELCQEAHSTILSI 216
Cdd:cd03183   81 ICEIMQPEAAGYDVFEGRPKLAAWRKRVKEA-GNPLFDEAHKVIYKL 126

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715  91 ARAQVHEYLGWHADNIRGTFGVLLWTKVLGPLIGVQ-VPQEKVERNRDRMVLVLQQLEDKFLRDRAFLVGQQVTLADLMS 169
Cdd:cd03183    1 KRARVDEYLAWQHTNLRLGCAAYFWQKVLLPLFGGTpVSPEKVKKAEENLEESLDLLENKFLKDKPFLAGDEISIADLSA 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 568966715 170 LEELMQPVALGYNLFEGRPQLTAWRERVEAFlGAELCQEAHSTILSI 216
Cdd:cd03183   81 ICEIMQPEAAGYDVFEGRPKLAAWRKRVKEA-GNPLFDEAHKVIYKL 126

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715   3 LELYLDLLSQPSRAVYIFAKKNGIPFQTRTVDILKGQHMSEQFSQVNCLNKVPVLKDGSFVLTESTAILIYLSSKYQVAd 82
Cdd:COG0625    2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPEP- 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715  83 HWYPADLQARAQVHEYLGWHADNIRGTFGVLLwtKVLGPligvQVPQEKVERNRDRMVLVLQQLEDKfLRDRAFLVGQQV 162
Cdd:COG0625   81 PLLPADPAARARVRQWLAWADGDLHPALRNLL--ERLAP----EKDPAAIARARAELARLLAVLEAR-LAGGPYLAGDRF 153

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 568966715 163 TLADLMSLEELMQPVALGYNLfEGRPQLTAWRERVEA 199
Cdd:COG0625  154 SIADIALAPVLRRLDRLGLDL-ADYPNLAAWLARLAA 189

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715   3 LELYLD--LLSQPSRAVYIFAKKNGIPFQTRTVDILKGQHMSEQFSQVNCLNKVPVLKDGSFVLTESTAILIYLSSKYQV 80
Cdd:PRK15113   6 ITLYSDahFFSPYVMSAFVALQEKGLPFELKTVDLDAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEERFAP 85

                         90       100
                 ....*....|....*....|...
gi 568966715  81 ADHW--YPADLQARAQVHEYLGW 101
Cdd:PRK15113  86 PAWEriYPADLQARARARQIQAW 108

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568966715  128 PQEKVERNRDRMVLVLQQLEDKfLRDRAFLVGQQVTLADLMSLEELMQPVALGYN-LFEGRPQLTAWRERVEA 199
Cdd:pfam00043  20 KEPEVDEALEKVARVLSALEEV-LKGQTYLVGDKLTLADIALAPALLWLYELDPAcLREKFPNLKAWFERVAA 91

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715  91 ARAQVHEYLGWHADNIRGTFGVLLWTKVLGPLIGVQ-VPQEKVERNRDRMVLVLQQLEDKFLRDRAFLVGQQVTLADLMS 169
Cdd:cd03183    1 KRARVDEYLAWQHTNLRLGCAAYFWQKVLLPLFGGTpVSPEKVKKAEENLEESLDLLENKFLKDKPFLAGDEISIADLSA 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 568966715 170 LEELMQPVALGYNLFEGRPQLTAWRERVEAFlGAELCQEAHSTILSI 216
Cdd:cd03183   81 ICEIMQPEAAGYDVFEGRPKLAAWRKRVKEA-GNPLFDEAHKVIYKL 126

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715   3 LELYLDLLSQPSRAVYIFAKKNGIPFQTRTVDILKGQHMSEQFSQVNCLNKVPVLKDGSFVLTESTAILIYLSSKYQVAd 82
Cdd:COG0625    2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPEP- 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715  83 HWYPADLQARAQVHEYLGWHADNIRGTFGVLLwtKVLGPligvQVPQEKVERNRDRMVLVLQQLEDKfLRDRAFLVGQQV 162
Cdd:COG0625   81 PLLPADPAARARVRQWLAWADGDLHPALRNLL--ERLAP----EKDPAAIARARAELARLLAVLEAR-LAGGPYLAGDRF 153

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 568966715 163 TLADLMSLEELMQPVALGYNLfEGRPQLTAWRERVEA 199
Cdd:COG0625  154 SIADIALAPVLRRLDRLGLDL-ADYPNLAAWLARLAA 189

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715   1 MGLELYLDLLSQPSRAVYIFAKKnGIPFQTRTVDILKGQHMSEQFSQVNCLNKVPVLKDGSFVLTESTAILIYLSSKY-- 78
Cdd:PLN02395   1 MVLKVYGPAFASPKRALVTLIEK-GVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKYrs 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715  79 QVADhWYPADLQARAQVHEYLGWHADNIRGTFGVLLWTKVLGPLIGVQVPQEKVERNRDRMVLVLQQLEDKfLRDRAFLV 158
Cdd:PLN02395  80 QGPD-LLGKTIEERGQVEQWLDVEATSYHPPLLNLTLHILFASKMGFPADEKVIKESEEKLAKVLDVYEAR-LSKSKYLA 157

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 568966715 159 GQQVTLADLMSL---EELMQPVALGYnLFEGRPQLTAW 193
Cdd:PLN02395 158 GDFVSLADLAHLpftEYLVGPIGKAY-LIKDRKHVSAW 194

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715   3 LELYLD--LLSQPSRAVYIFAKKNGIPFQTRTVDILKGQHMSEQFSQVNCLNKVPVLKDGSFVLTESTAILIYLSSKYQV 80
Cdd:PRK15113   6 ITLYSDahFFSPYVMSAFVALQEKGLPFELKTVDLDAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEERFAP 85

                         90       100
                 ....*....|....*....|...
gi 568966715  81 ADHW--YPADLQARAQVHEYLGW 101
Cdd:PRK15113  86 PAWEriYPADLQARARARQIQAW 108

GST_N family, Class Phi subfamily; composed of plant-specific class Phi GSTs and related fungal and bacterial 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. 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 Phi GST subfamily has experience extensive gene duplication. The Arabidopsis and Oryza genomes contain 13 and 16 Phi GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Tau GSTs, showing class specificity in substrate preference. Phi enzymes are highly reactive toward chloroacetanilide and thiocarbamate herbicides. Some Phi GSTs have other functions including transport of flavonoid pigments to the vacuole, shoot regeneration and GSH peroxidase activity.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568966715   3 LELYLDLLSQPSRAVYIFAKKNGIPFQTRTVDILKGQHMSEQFSQVNCLNKVPVLKDGSFVLTESTAILIYLSSK 77
Cdd:cd03053    2 LKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAEK 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
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568966715  25 GIPFQTRTVDILKGQHMSEQFSQVNCLNKVPVLKDGSFVLTESTAILIYLSSKY 78
Cdd:cd03046   22 GLPYELVLYDRGPGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEKY 75

GST_N family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. cerevisiae GST protein, GTT2. 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. GTT2, a homodimer, exhibits GST activity with standard substrates. Strains with deleted GTT2 genes are viable but exhibit increased sensitivity to heat shock.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568966715   3 LELYlDLLSQP-SRAVYIFAKKNGIPFQTRTVDILKGQHMSEQFSQVNCLNKVPVLK--DGSFvLTESTAILIYL 74
Cdd:cd03051    1 MKLY-DSPTAPnPRRVRIFLAEKGIDVPLVTVDLAAGEQRSPEFLAKNPAGTVPVLEldDGTV-ITESVAICRYL 73

GST_N family, Class Beta 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. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit limited GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they also bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568966715  14 SRAVYIFAKKNGIPFQTRTVDILKGQHMSEQFSQVNCLNKVPVL--KDGSfVLTESTAILIYL 74
Cdd:cd03057   11 SLAPHIALEELGLPFELVRVDLRTKTQKGADYLAINPKGQVPALvlDDGE-VLTESAAILQYL 72

putative S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715  33 VDILKGQHMSEQFSQVNCLNKVPVLKDGS----FVLTESTAILIYLSSKYqvaDHWYPADLQARAqvhEYLGWhadnirg 108
Cdd:PRK11752  80 IRIGEGDQFSSGFVEINPNSKIPALLDRSgnppIRVFESGAILLYLAEKF---GAFLPKDLAART---ETLNW------- 146

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568966715 109 tfgvLLWTKVLGPLIG-------VQVPqEKVERNRDRMVL-VLQQLE--DKFLRDRAFLVGQQVTLADL 167
Cdd:PRK11752 147 ----LFWQQGSAPFLGggfghfyAYAP-EKIEYAINRFTMeAKRQLDvlDKQLAEHEYIAGDEYTIADI 210

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 568966715  95 VHEYLGWHADNIRGTFGVLLWTKVLGPligvQVPQEKVERNRDRMVLVLQQLEdKFLRDRAFLVGQQVTLADLM--SLEE 172
Cdd:cd00299    1 VRALEDWADATLAPPLVRLLYLEKVPL----PKDEAAVEAAREELPALLAALE-QLLAGRPYLAGDQFSLADVAlaPVLA 75

                         90       100
                 ....*....|....*....|....*
gi 568966715 173 LMQPVALGYNLFEGRPQLTAWRERV 197
Cdd:cd00299   76 RLEALGPYYDLLDEYPRLKAWYDRL 100

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568966715   14 SRAVYIFAKKNGIPFQTRTVDiLKGQHMSEQFSQVNCLNKVPVLKD-GSFVLTESTAILIYL 74
Cdd:pfam13409   5 SHRVRLALEEKGLPYEIELVD-LDPKDKPPELLALNPLGTVPVLVLpDGTVLTDSLVILEYL 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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715 124 GVQVPQEKVERnrdrmvlVLQQLE--DKFLRDRAFLVGQQVTLADLMSLEELMQPVALGYNLfEGRPQLTAWRERVEAFL 201
Cdd:cd03177   32 GAEPPEEKLDK-------LEEALEflETFLEGSDYVAGDQLTIADLSLVATVSTLEVVGFDL-SKYPNVAAWYERLKALP 103

                         90
                 ....*....|
gi 568966715 202 -GAELCQEAH 210
Cdd:cd03177  104 pGEEENGEGA 113

C-terminal, alpha helical domain of GTT2-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the Saccharomyces cerevisiae GST protein, GTT2. 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. GTT2, a homodimer, exhibits GST activity with standard substrates. Strains with deleted GTT2 genes are viable but exhibit increased sensitivity to heat shock.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715 116 TKVLGPLIGVQVPqEKVERNRDRmVLVLQQLEDKFLRDRAFLVGQQVTLADLMSLEELMQPVALGYNLFEGRPQLTAWRE 195
Cdd:cd03182   31 TPGLKPDREVQVP-EWGERNKKR-VIDFLPVLDKRLAESPYVAGDRFSIADITAFVALDFAKNLKLPVPEELTALRRWYE 108

                 ....
gi 568966715 196 RVEA 199
Cdd:cd03182  109 RMAA 112

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568966715  91 ARAQVHEYLGWHADNIrgtfgVLLWTKVLGPLIGV-QVPQEKVERNRDRMVLVLQQLEdKFLRDRAFLVGQQVTLADLM 168
Cdd:cd03181    1 EAAQVLQWISFANSEL-----LPAAATWVLPLLGIaPYNKKAVDKAKEDLKRALGVLE-EHLLTRTYLVGERITLADIF 73

GSH-dependent disulfide bond oxidoreductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715   7 LDLLSQPS---RAVYIFAKKNGIPFQTRTVDILKGQHMSEQFSQVNCLNKVPVLKDGS-------FVLTESTAILIYLSS 76
Cdd:PRK13972   2 IDLYFAPTpngHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDHSpadggepLSLFESGAILLYLAE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715  77 KYQVadhWYPADLQARAQVHEYLGWHADNirgtfgvllwtkvLGPLIGVQ------VPQ------EKVERNRDRMVLVLq 144
Cdd:PRK13972  82 KTGL---FLSHETRERAATLQWLFWQVGG-------------LGPMLGQNhhfnhaAPQtipyaiERYQVETQRLYHVL- 144

                        170       180
                 ....*....|....*....|...
gi 568966715 145 qleDKFLRDRAFLVGQQVTLADL 167
Cdd:PRK13972 145 ---NKRLENSPWLGGENYSIADI 164

C-terminal, alpha helical domain of Class Phi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Phi subfamily; composed of plant-specific class Phi GSTs and related fungal and bacterial 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. 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 Phi GST subfamily has experience extensive gene duplication. The Arabidopsis and Oryza genomes contain 13 and 16 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Tau GSTs, showing class specificity in substrate preference. Phi enzymes are highly reactive toward chloroacetanilide and thiocarbamate herbicides. Some Phi GSTs have other functions including transport of flavonoid pigments to the vacuole, shoot regeneration and GSH peroxidase activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966715 113 LLWTKVLGPLIGVQVPQEKVERNRDRMVLVLQQLEDKfLRDRAFLVGQQVTLADLMSLEELMQPVALGYN-LFEGRPQLT 191
Cdd:cd03187   24 LVFELVFKPMLGLKTDEAVVEENEAKLKKVLDVYEAR-LSKSKYLAGDSFTLADLSHLPNLHYLMATPSKkLFDSRPHVK 102

                 ....*...
gi 568966715 192 AWRERVEA 199
Cdd:cd03187  103 AWWEDISA 110

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 568966715  91 ARAQVHEYLGWHADNIRGTFGVLLWTKVLGPligVQVPQEkVERNRDRMVLVLQQLeDKFLRDRAFLVGQQVTLADLMSL 170
Cdd:cd03178    1 ERAEVLQWLFFQMSGLGPMFGQAGHFLYFAP---EKIPYA-IERYTDEVKRLYGVL-DKRLSDRPYLAGEEYSIADIALY 75

                         90       100
                 ....*....|....*....|....*....
gi 568966715 171 EELMQPVALGYNLFEGRPQLTAWRERVEA 199
Cdd:cd03178   76 PWTHYADLGGFADLSEYPNVKRWLERIAA 104

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568966715  14 SRAVYIFAKKNGIPFQTRTVDiLKGQHMSEQFSQVNCLNKVPVLK--DGsFVLTESTAILIYLSSK 77
Cdd:cd03044   12 SLKILAAAKYNGLDVEIVDFQ-PGKENKTPEFLKKFPLGKVPAFEgaDG-FCLFESNAIAYYVANL 75

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568966715  16 AVYIFAKKNGIPFQTRTVDILkgqHMSEQfsqvnclNKVPVLKDGSFVLTESTAILIYLSSK 77
Cdd:cd03054   21 KVETYLRMAGIPYEVVFSSNP---WRSPT-------GKLPFLELNGEKIADSEKIIEYLKKK 72