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 702760663  91 ARARVHEYLGWHADCIRGTFGIPLWVQVLGPLIGVQ-VPKEKVERNRTAMDQALQWLEDKFLGDRPFLAGQQVTLADLMA 169
Cdd:cd03183    1 KRARVDEYLAWQHTNLRLGCAAYFWQKVLLPLFGGTpVSPEKVKKAEENLEESLDLLENKFLKDKPFLAGDEISIADLSA 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 702760663 170 LEELMQPVALGYELFEGRPRLAAWRGRVEAFlGAELCQEAHSIILSI 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 702760663  91 ARARVHEYLGWHADCIRGTFGIPLWVQVLGPLIGVQ-VPKEKVERNRTAMDQALQWLEDKFLGDRPFLAGQQVTLADLMA 169
Cdd:cd03183    1 KRARVDEYLAWQHTNLRLGCAAYFWQKVLLPLFGGTpVSPEKVKKAEENLEESLDLLENKFLKDKPFLAGDEISIADLSA 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 702760663 170 LEELMQPVALGYELFEGRPRLAAWRGRVEAFlGAELCQEAHSIILSI 216
Cdd:cd03183   81 ICEIMQPEAAGYDVFEGRPKLAAWRKRVKEA-GNPLFDEAHKVIYKL 126

GST_N family, Class Theta subfamily; composed of eukaryotic class Theta GSTs and bacterial dichloromethane (DCM) dehalogenase. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Mammalian class Theta GSTs show poor GSH conjugating activity towards the standard substrates, CDNB and ethacrynic acid, differentiating them from other mammalian GSTs. GSTT1-1 shows similar cataytic activity as bacterial DCM dehalogenase, catalyzing the GSH-dependent hydrolytic dehalogenation of dihalomethanes. This is an essential process in methylotrophic bacteria to enable them to use chloromethane and DCM as sole carbon and energy sources. The presence of polymorphisms in human GSTT1-1 and its relationship to the onset of diseases including cancer is subject of many studies. Human GSTT2-2 exhibits a highly specific sulfatase activity, catalyzing the cleavage of sulfate ions from aralkyl sufate esters, but not from aryl or alkyl sulfate esters.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 702760663   3 LELFLDLVSQPSRAVYIFAKKNGIPLELRTVDLVKGQHKSKEFLQINSLGKLPTLKDGDFILTESSAILIYLSCKY 78
Cdd:cd03050    1 LKLYYDLMSQPSRAVYIFLKLNKIPFEECPIDLRKGEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 702760663   1 MGLELFLDLVSQPSRAVYIFAKKnGIPLELRTVDLVKGQHKSKEFLQINSLGKLPTLKDGDFILTESSAILIYLSCKY-- 78
Cdd:PLN02395   1 MVLKVYGPAFASPKRALVTLIEK-GVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKYrs 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 702760663  79 QTPDhWYPSDLQARARVHEYLGWHADcirgTFGIPLWVQVL----GPLIGVQVPKEKVERNRTAMDQALQWLEDKfLGDR 154
Cdd:PLN02395  80 QGPD-LLGKTIEERGQVEQWLDVEAT----SYHPPLLNLTLhilfASKMGFPADEKVIKESEEKLAKVLDVYEAR-LSKS 153

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 702760663 155 PFLAGQQVTLADLMAL---EELMQPVALGYeLFEGRPRLAAW 193
Cdd:PLN02395 154 KYLAGDFVSLADLAHLpftEYLVGPIGKAY-LIKDRKHVSAW 194

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 702760663  132 VERNRTAMDQALQWLEDkFLGDRPFLAGQQVTLADLMA--LEELMQPVALGYELFEGRPRLAAWRGR 196
Cdd:pfam13410   2 LERAREQLRAALDALEA-RLADGPGLLGDRPTLADIALapVLARLDAAYPGLDLREGYPRLRAWLER 67

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 702760663  91 ARARVHEYLGWHADCIRGTFGIPLWVQVLGPLIGVQ-VPKEKVERNRTAMDQALQWLEDKFLGDRPFLAGQQVTLADLMA 169
Cdd:cd03183    1 KRARVDEYLAWQHTNLRLGCAAYFWQKVLLPLFGGTpVSPEKVKKAEENLEESLDLLENKFLKDKPFLAGDEISIADLSA 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 702760663 170 LEELMQPVALGYELFEGRPRLAAWRGRVEAFlGAELCQEAHSIILSI 216
Cdd:cd03183   81 ICEIMQPEAAGYDVFEGRPKLAAWRKRVKEA-GNPLFDEAHKVIYKL 126

GST_N family, Class Theta subfamily; composed of eukaryotic class Theta GSTs and bacterial dichloromethane (DCM) dehalogenase. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Mammalian class Theta GSTs show poor GSH conjugating activity towards the standard substrates, CDNB and ethacrynic acid, differentiating them from other mammalian GSTs. GSTT1-1 shows similar cataytic activity as bacterial DCM dehalogenase, catalyzing the GSH-dependent hydrolytic dehalogenation of dihalomethanes. This is an essential process in methylotrophic bacteria to enable them to use chloromethane and DCM as sole carbon and energy sources. The presence of polymorphisms in human GSTT1-1 and its relationship to the onset of diseases including cancer is subject of many studies. Human GSTT2-2 exhibits a highly specific sulfatase activity, catalyzing the cleavage of sulfate ions from aralkyl sufate esters, but not from aryl or alkyl sulfate esters.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 702760663   3 LELFLDLVSQPSRAVYIFAKKNGIPLELRTVDLVKGQHKSKEFLQINSLGKLPTLKDGDFILTESSAILIYLSCKY 78
Cdd:cd03050    1 LKLYYDLMSQPSRAVYIFLKLNKIPFEECPIDLRKGEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 702760663  16 AVYIFAKKNGIPLELRTVDLVKGQHKSKEFLQINSLGKLPTLKDGDFILTESSAILIYLSCKYQTPDHW--YPSDLQARA 93
Cdd:PRK15113  21 SAFVALQEKGLPFELKTVDLDAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEERFAPPAWEriYPADLQARA 100

                 ....*...
gi 702760663  94 RVHEYLGW 101
Cdd:PRK15113 101 RARQIQAW 108

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 702760663   1 MGLELFLDLVSQPSRAVYIFAKKnGIPLELRTVDLVKGQHKSKEFLQINSLGKLPTLKDGDFILTESSAILIYLSCKY-- 78
Cdd:PLN02395   1 MVLKVYGPAFASPKRALVTLIEK-GVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKYrs 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 702760663  79 QTPDhWYPSDLQARARVHEYLGWHADcirgTFGIPLWVQVL----GPLIGVQVPKEKVERNRTAMDQALQWLEDKfLGDR 154
Cdd:PLN02395  80 QGPD-LLGKTIEERGQVEQWLDVEAT----SYHPPLLNLTLhilfASKMGFPADEKVIKESEEKLAKVLDVYEAR-LSKS 153

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 702760663 155 PFLAGQQVTLADLMAL---EELMQPVALGYeLFEGRPRLAAW 193
Cdd:PLN02395 154 KYLAGDFVSLADLAHLpftEYLVGPIGKAY-LIKDRKHVSAW 194

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 702760663   3 LELFLDLVSQPSRAVYIFAKKNGIPLELRTVDLVKGQHKSKEFLQINSLGKLPTLKDGDFILTESSAILIYLSCK 77
Cdd:cd03053    2 LKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAEK 76

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 702760663  17 VYIFAKKNGIPLELRTVDLVKGQHKSKEFLQINSLGKLPTLKD---GDFILTESSAILIYLSCKYQT 80
Cdd:cd03048   15 VSIMLEELGLPYEIHPVDISKGEQKKPEFLKINPNGRIPAIVDhngTPLTVFESGAILLYLAEKYDK 81

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 702760663   5 LFLDLVSQP-SRAVYIFAKKNGIPLELRTVDLVKGQHKSKEFLQINSLGKLPTLK--DGDFIlTESSAILIYL 74
Cdd:cd03051    2 KLYDSPTAPnPRRVRIFLAEKGIDVPLVTVDLAAGEQRSPEFLAKNPAGTVPVLEldDGTVI-TESVAICRYL 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 702760663  14 SRAVYIFAKKNGIPLELRTVDLVKGQHKSKEFLQINSLGKLPTLKDGD-FILTESSAILIYL 74
Cdd:cd03057   11 SLAPHIALEELGLPFELVRVDLRTKTQKGADYLAINPKGQVPALVLDDgEVLTESAAILQYL 72

Glutathione S-transferase, N-terminal domain; Function: conjugation of reduced glutathione to a variety of targets. Also included in the alignment, but not GSTs: S-crystallins from squid (similarity to GST previously noted); eukaryotic elongation factors 1-gamma (not known to have GST activity and similarity not previously recognized); HSP26 family of stress-related proteins including auxin-regulated proteins in plants and stringent starvation proteins in E. coli (not known to have GST activity and similarity not previously recognized). The glutathione molecule binds in a cleft between the N- and C-terminal domains - the catalytically important residues are proposed to reside in the N-terminal domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 702760663   25 GIPLELRTVDLVKGQHKSKEFLQINSLGKLPTLKDGDFILTESSAILIYL 74
Cdd:pfam02798  25 GVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYI 74

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 702760663  95 VHEYLGWHADCIRGTFGIPLWVQVLGPligvQVPKEKVERNRTAMDQALQWLEdKFLGDRPFLAGQQVTLADLMALEEL- 173
Cdd:cd00299    1 VRALEDWADATLAPPLVRLLYLEKVPL----PKDEAAVEAAREELPALLAALE-QLLAGRPYLAGDQFSLADVALAPVLa 75

                         90       100
                 ....*....|....*....|....*
gi 702760663 174 -MQPVALGYELFEGRPRLAAWRGRV 197
Cdd:cd00299   76 rLEALGPYYDLLDEYPRLKAWYDRL 100

putative S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 702760663  33 VDLVKGQHKSKEFLQINSLGKLPTLKD--GD--FILTESSAILIYLSCKYqtpDHWYPSDLQARArvhEYLGWHadcirg 108
Cdd:PRK11752  80 IRIGEGDQFSSGFVEINPNSKIPALLDrsGNppIRVFESGAILLYLAEKF---GAFLPKDLAART---ETLNWL------ 147

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 702760663 109 tfgipLWVQVLGPLIG-------VQVPkEKVER--NRTAMDQALQW-LEDKFLGDRPFLAGQQVTLADlMA 169
Cdd:PRK11752 148 -----FWQQGSAPFLGggfghfyAYAP-EKIEYaiNRFTMEAKRQLdVLDKQLAEHEYIAGDEYTIAD-IA 211

GST_N family, unknown subfamily 2; composed of uncharacterized bacterial proteins with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The sequence from Burkholderia cepacia was identified as part of a gene cluster involved in the degradation of 2,4,5-trichlorophenoxyacetic acid. Some GSTs (e.g. Class Zeta and Delta) are known to catalyze dechlorination reactions.

                         10        20        30
                 ....*....|....*....|....*....|..
gi 702760663  44 EFLQINSLGKLPTLKDGDFILTESSAILIYLS 75
Cdd:cd03047   42 EFLAMNPNGRVPVLEDGDFVLWESNAILRYLA 73

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 702760663 112 IPLWVQVLGPLIGV-QVPKEKVERNRTAMDQALQWLEDKFLgDRPFLAGQQVTLADLMA 169
Cdd:cd03181   17 LPAAATWVLPLLGIaPYNKKAVDKAKEDLKRALGVLEEHLL-TRTYLVGERITLADIFV 74

C-terminal, alpha helical domain of Class Beta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they are involved in the protection against oxidative stress and are able to bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs, contributing to antibiotic resistance. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH. One member of this subfamily is a GST from Burkholderia xenovorans LB400 that is encoded by the bphK gene and is part of the biphenyl catabolic pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 702760663  91 ARARVHEYLGWHADCIRGTFGIPLWVQVLGPLIGVQVPKEKVernRTAMDQALQWLEDKfLGDRPFLAGQQVTLADLMAL 170
Cdd:cd03188    2 ERARLLEWLNFIASELHKAFGPLFYPARWADDALAEEVKAAA---RERLERRLAYLDAQ-LAGGPYLLGDQFSVADAYLF 77

                         90       100
                 ....*....|....*....|....*....
gi 702760663 171 EELMQPVALGYELfEGRPRLAAWRGRVEA 199
Cdd:cd03188   78 VVLRWARAVGLDL-SDWPHLAAYLARVAA 105

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 702760663  98 YLGWHAdCIRGTFGIPLWVQVLGPLIGVQVPKEKVERNRTAMDQALQWLEDKfLGDRPFLAGQQVTLADLMALEELMQPV 177
Cdd:cd03207    1 YLRWLF-FAAGTVEPPLLNKALGRFFEPPWGEPAIAAAYGDLDERLAALEAA-LAGRPYLVGERFSAADLLLASVLRWAR 78

                         90       100
                 ....*....|....*....|..
gi 702760663 178 ALGyeLFEGRPRLAAWRGRVEA 199
Cdd:cd03207   79 AFG--LLPEYPALRAYVARCTA 98

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 702760663   8 DLVSQPSRAVyiFAKKnGIPLELRTVDLvkgQHKSKEFLQINSLGKLPTLKDGDFILTESSAILIYLSCKY 78
Cdd:cd03059    9 DVYSHRVRIV--LAEK-GVSVEIIDVDP---DNPPEDLAELNPYGTVPTLVDRDLVLYESRIIMEYLDERF 73

GSH-dependent disulfide bond oxidoreductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 702760663   7 LDLVSQPS---RAVYIFAKKNGIPLELRTVDLVKGQHKSKEFLQINSLGKLPTLKDGD-------FILTESSAILIYLSC 76
Cdd:PRK13972   2 IDLYFAPTpngHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDHSpadggepLSLFESGAILLYLAE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 702760663  77 KYQTpdhWYPSDLQARARVHEYLGWHadcirgtfgiplwVQVLGPLIGV---------QVPKEKVERNRTAMdQALQWLE 147
Cdd:PRK13972  82 KTGL---FLSHETRERAATLQWLFWQ-------------VGGLGPMLGQnhhfnhaapQTIPYAIERYQVET-QRLYHVL 144

                        170       180
                 ....*....|....*....|
gi 702760663 148 DKFLGDRPFLAGQQVTLADL 167
Cdd:PRK13972 145 NKRLENSPWLGGENYSIADI 164

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 702760663 126 QVPKEKVERNRTAMDQALQ-WLE--DKFLGD--RPFLAGQQVTLADLMALEELMQP-VALGYELFEGRPRLAAWRGRV 197
Cdd:cd03192   27 PDGEEKKEKKKEFLEEALPkFLGkfEKILKKsgGGYFVGDKLTWADLALFDVLDYLlYLLPKDLLEKYPKLKALRERV 104

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 702760663 140 DQALQWLEDKfLGDRPFLAGQQVTLADLM---ALEElmqpVALGYELFEGRPRLAAWRGRVEA 199
Cdd:cd03189   64 KRHLDFLEDH-LAKHPYFAGDELTAADIMmsfPLEA----ALARGPLLEQYPNIAAYLERIEA 121

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
                 ....*....|....*....|....*..
gi 702760663 141 QALQWLEDKfLGDRPFLAGQQVTLADL 167
Cdd:cd03190   44 EALDKLEKR-LSKQPYLLGDRLTEADI 69