maleylacetoacetate isomerase; Maleylacetoacetate isomerase is an enzyme of tyrosine and phenylalanine catabolism. It requires glutathione and belongs by homology to the zeta family of glutathione S-transferases. The enzyme (EC 5.2.1.2) is described as active also on maleylpyruvate, and the example from a Ralstonia sp. catabolic plasmid is described as a maleylpyruvate isomerase involved in gentisate catabolism. [Energy metabolism, Amino acids and amines]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949    13 KLYSYWRSSCAHRVRIALTLKGLDYEYIPVNLLK-GDQSDSDFKKINPMGTVPALVDGDVVINDSFAIIMYLDDKYPEPP 91
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLLRdGEQRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETYPDPP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949    92 LLPSDYHKRAVNYQATSIVMSGIQPHQNMALFRYLEDKIN--AEEKTAWITNAITKGFTALEKLLVSCAGKYATGDEVYL 169
Cdd:TIGR01262  81 LLPADPIKRARVRALALLIACDIHPLNNLRVLQYLREKLGveEEARNRWYQHWISKGFAALEALLQPHAGRFCVGDTPTL 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 15226949   170 ADLFLAPQIHAAfNRFHINMEPFPTLARFYESYNELPAFQNAVPEKQPDTP 220
Cdd:TIGR01262 161 ADLCLVPQVYNA-ERFGVDLTPYPTLRRIAAALAALPAFQRAHPENQPDTP 210

maleylacetoacetate isomerase; Maleylacetoacetate isomerase is an enzyme of tyrosine and phenylalanine catabolism. It requires glutathione and belongs by homology to the zeta family of glutathione S-transferases. The enzyme (EC 5.2.1.2) is described as active also on maleylpyruvate, and the example from a Ralstonia sp. catabolic plasmid is described as a maleylpyruvate isomerase involved in gentisate catabolism. [Energy metabolism, Amino acids and amines]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949    13 KLYSYWRSSCAHRVRIALTLKGLDYEYIPVNLLK-GDQSDSDFKKINPMGTVPALVDGDVVINDSFAIIMYLDDKYPEPP 91
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLLRdGEQRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETYPDPP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949    92 LLPSDYHKRAVNYQATSIVMSGIQPHQNMALFRYLEDKIN--AEEKTAWITNAITKGFTALEKLLVSCAGKYATGDEVYL 169
Cdd:TIGR01262  81 LLPADPIKRARVRALALLIACDIHPLNNLRVLQYLREKLGveEEARNRWYQHWISKGFAALEALLQPHAGRFCVGDTPTL 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 15226949   170 ADLFLAPQIHAAfNRFHINMEPFPTLARFYESYNELPAFQNAVPEKQPDTP 220
Cdd:TIGR01262 161 ADLCLVPQVYNA-ERFGVDLTPYPTLRRIAAALAALPAFQRAHPENQPDTP 210

C-terminal, alpha helical domain of Class Zeta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Zeta 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. Class Zeta GSTs, also known as maleylacetoacetate (MAA) isomerases, catalyze the isomerization of MAA to fumarylacetoacetate, the penultimate step in tyrosine/phenylalanine catabolism, using GSH as a cofactor. They show little GSH-conjugating activity towards traditional GST substrates, but display modest GSH peroxidase activity. They are also implicated in the detoxification of the carcinogen dichloroacetic acid by catalyzing its dechlorination to glyoxylic acid.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949  98 HKRAVNYQATSIVMSGIQPHQNMALFRYLEDKINA--EEKTAWITNAITKGFTALEKLLVSCAGKYATGDEVYLADLFLA 175
Cdd:cd03191   2 KKRARVRAIALIIACDIHPLQNLRVLKYLTEKLGVseEEKLAWAQHWIERGFQALEKLLASTAGKYCVGDEPTLADICLV 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 15226949 176 PQIHAAfNRFHINMEPFPTLARFYESYNELPAFQNAVPEKQ 216
Cdd:cd03191  82 PQVYNA-RRFGVDLSPYPTIVRINEACLELPAFQAAHPENQ 121

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949   21 SCAHRVRIALTLKGLDYEYIPVNLLKGDQSDSDFKKINPMGTVPALVDGDVVINDSFAIIMYLDDKYPE--PPLLPSDYH 98
Cdd:PLN02395  11 ASPKRALVTLIEKGVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKYRSqgPDLLGKTIE 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949   99 KRAVNYQATSIVMSGIQPH-QNMALFRYLEDKI----------NAEEKTAWITNAITkgftalEKLLVScagKYATGDEV 167
Cdd:PLN02395  91 ERGQVEQWLDVEATSYHPPlLNLTLHILFASKMgfpadekvikESEEKLAKVLDVYE------ARLSKS---KYLAGDFV 161

                 ....*
gi 15226949  168 YLADL 172
Cdd:PLN02395 162 SLADL 166

maleylacetoacetate isomerase; Maleylacetoacetate isomerase is an enzyme of tyrosine and phenylalanine catabolism. It requires glutathione and belongs by homology to the zeta family of glutathione S-transferases. The enzyme (EC 5.2.1.2) is described as active also on maleylpyruvate, and the example from a Ralstonia sp. catabolic plasmid is described as a maleylpyruvate isomerase involved in gentisate catabolism. [Energy metabolism, Amino acids and amines]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949    13 KLYSYWRSSCAHRVRIALTLKGLDYEYIPVNLLK-GDQSDSDFKKINPMGTVPALVDGDVVINDSFAIIMYLDDKYPEPP 91
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLLRdGEQRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETYPDPP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949    92 LLPSDYHKRAVNYQATSIVMSGIQPHQNMALFRYLEDKIN--AEEKTAWITNAITKGFTALEKLLVSCAGKYATGDEVYL 169
Cdd:TIGR01262  81 LLPADPIKRARVRALALLIACDIHPLNNLRVLQYLREKLGveEEARNRWYQHWISKGFAALEALLQPHAGRFCVGDTPTL 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 15226949   170 ADLFLAPQIHAAfNRFHINMEPFPTLARFYESYNELPAFQNAVPEKQPDTP 220
Cdd:TIGR01262 161 ADLCLVPQVYNA-ERFGVDLTPYPTLRRIAAALAALPAFQRAHPENQPDTP 210

C-terminal, alpha helical domain of Class Zeta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Zeta 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. Class Zeta GSTs, also known as maleylacetoacetate (MAA) isomerases, catalyze the isomerization of MAA to fumarylacetoacetate, the penultimate step in tyrosine/phenylalanine catabolism, using GSH as a cofactor. They show little GSH-conjugating activity towards traditional GST substrates, but display modest GSH peroxidase activity. They are also implicated in the detoxification of the carcinogen dichloroacetic acid by catalyzing its dechlorination to glyoxylic acid.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949  98 HKRAVNYQATSIVMSGIQPHQNMALFRYLEDKINA--EEKTAWITNAITKGFTALEKLLVSCAGKYATGDEVYLADLFLA 175
Cdd:cd03191   2 KKRARVRAIALIIACDIHPLQNLRVLKYLTEKLGVseEEKLAWAQHWIERGFQALEKLLASTAGKYCVGDEPTLADICLV 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 15226949 176 PQIHAAfNRFHINMEPFPTLARFYESYNELPAFQNAVPEKQ 216
Cdd:cd03191  82 PQVYNA-RRFGVDLSPYPTIVRINEACLELPAFQAAHPENQ 121

Glutathione S-transferase (GST) family, N-terminal 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 subfamily, a member of the DsbA family). 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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, metaxin 2 and stringent starvation protein A.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15226949  12 LKLYSYWRSSCAHRVRIALTLKGLDYEYIPVNLLKGDQSDsdFKKINPMGTVPALVDGDVVINDSFAIIMYLD 84
Cdd:cd00570   1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQEE--FLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

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 15226949  11 KLKLYSYWRSSCAHRVRIALTLKGLDYEYIPVNLLKGDQSDSDFKKINPMGTVPALVDGDVVINDSFAIIMYLDDK 86
Cdd:cd03053   1 VLKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAEK 76

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15226949    14 LYSYWRSSCAHRVRIALTLKGLDYEYIPVNLlkgDQSDSDFKKINPMGTVPALVDGDVVINDSFAIIMYLDDKYPEPP 91
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIPP---GDHPPELLAKNPLGKVPVLEDDGGILCESLAIIDYLEELYPGPP 75

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15226949    10 AKLKLYSYWRSSCAHRVRIALTLKGLDYEYIPVNLLKGDQSDSDFKKINPMGTVPALVDGDVVINDSFAIIMYLDD 85
Cdd:pfam02798   1 MVLTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15226949  12 LKLYsYWRSSCAHRVRIALTLKGLDYEYIPVNLLKGDQSDSDFKKINPMGTVPALVDGD-VVINDSFAIIMYLDDKYP 88
Cdd:cd03057   1 MKLY-YSPGACSLAPHIALEELGLPFELVRVDLRTKTQKGADYLAINPKGQVPALVLDDgEVLTESAAILQYLADLHP 77

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 15226949  12 LKLYSYWRSSCAHRVRIALTLKGLDYEYIPVNLLKGDQSDSDFKKINPMGTVPALV-DGDVVINDSFAIIMYLD 84
Cdd:cd03051   1 MKLYDSPTAPNPRRVRIFLAEKGIDVPLVTVDLAAGEQRSPEFLAKNPAGTVPVLElDDGTVITESVAICRYLE 74

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 15226949  12 LKLYSYWRSSCAHRVRIALTLKGLDYEYIPVNLLKGDQSDSDFKKINPMGTVPALVDGDVVINDSFAIIMYLDDKY 87
Cdd:cd03050   1 LKLYYDLMSQPSRAVYIFLKLNKIPFEECPIDLRKGEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949    9 QAKLKLYS--YWRSSCAHRVRIALTLKGLDYEYIPVNLLKGDQSDSDFKKINPMGTVPALVDGDVVINDSFAIIMYLDDK 86
Cdd:PRK15113   3 KPAITLYSdaHFFSPYVMSAFVALQEKGLPFELKTVDLDAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEER 82

                         90
                 ....*....|....*...
gi 15226949   87 YPEPP---LLPSDYHKRA 101
Cdd:PRK15113  83 FAPPAwerIYPADLQARA 100

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 15226949  12 LKLYSYWRSSCAHRVRIALTLKGLDYEYIPVNLlkgDQSDSDFKKINPMGTVPALVDGDVVINDSFAIIMYLDDKY 87
Cdd:cd03059   1 MTLYSGPDDVYSHRVRIVLAEKGVSVEIIDVDP---DNPPEDLAELNPYGTVPTLVDRDLVLYESRIIMEYLDERF 73

GST_N family, Beta etherase LigE subfamily; composed of proteins similar to Sphingomonas paucimobilis beta etherase, LigE, a GST-like protein that catalyzes the cleavage of the beta-aryl ether linkages present in low-moleculer weight lignins using GSH as the hydrogen donor. This reaction is an essential step in the degradation of lignin, a complex phenolic polymer that is the most abundant aromatic material in the biosphere. The beta etherase activity of LigE is enantioselective and it complements the activity of the other GST family beta etherase, LigF.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949  25 RVRIALTLKGLDYEYIPVNL-----LKGDQSDSDFKkinpmgTVPALVDGD-VVINDSFAIIMYLDDKYP 88
Cdd:cd03038  21 KTRLALNHKGLEYKTVPVEFpdippILGELTSGGFY------TVPVIVDGSgEVIGDSFAIAEYLEEAYP 84

glutathione S-transferase DHAR1

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949   22 CAHRVRIALTL--KGLDYEYIPVNLLKGDQSdsdFKKINPMGTVPALVDGDVVINDSFAIIMYLDDKYPEPPL-LPSDYH 98
Cdd:PLN02378  20 CPFSQRALLTLeeKSLTYKIHLINLSDKPQW---FLDISPQGKVPVLKIDDKWVTDSDVIVGILEEKYPDPPLkTPAEFA 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949   99 KRAVNYQATsivmsgiqphqnMALFRYLEDKINAEEktawitNAITKGFTALEKLLVSCAGKYATGDEVYLADLFLAPQI 178
Cdd:PLN02378  97 SVGSNIFGT------------FGTFLKSKDSNDGSE------HALLVELEALENHLKSHDGPFIAGERVSAVDLSLAPKL 158

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 15226949  179 H------AAFNRFHINmEPFPTLARFYESYNELPAFQNAVPEKQ 216
Cdd:PLN02378 159 YhlqvalGHFKSWSVP-ESFPHVHNYMKTLFSLDSFEKTKTEEK 201

putative S-transferase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15226949   28 IALTLKGLDYEYIPVNLLKGDQSDSDFKKINPMGTVPALVD--GD--VVINDSFAIIMYLDDKYPEppLLPSDYHKRA 101
Cdd:PRK11752  66 LALGVKGAEYDAWLIRIGEGDQFSSGFVEINPNSKIPALLDrsGNppIRVFESGAILLYLAEKFGA--FLPKDLAART 141

GST_N family, Class Omega subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. They contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism. Polymorphisms of the class Omega GST genes may be associated with the development of some types of cancer and the age-at-onset of both Alzheimer's and Parkinson's diseases.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15226949  10 AKLKLYSYWRSSCAHRVRIALTLKGLDYEYIPVNLlkGDQSDSDFKKiNPMGTVPAL-VDGDVVINDSFAIIMYLD 84
Cdd:cd03055  17 GIIRLYSMRFCPYAQRARLVLAAKNIPHEVININL--KDKPDWFLEK-NPQGKVPALeIDEGKVVYESLIICEYLD 89

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949   12 LKLYSYWRSSCAHRVRIALTLKGLDYEYIPVNLLKGDQSDSDFKKINPMGTVPALVDGDVVINDSFAIIMYLDDKYPE-- 89
Cdd:PLN02473   3 VKVYGQIKAANPQRVLLCFLEKGIEFEVIHVDLDKLEQKKPEHLLRQPFGQVPAIEDGDLKLFESRAIARYYATKYADqg 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949   90 PPLLPSDYHKRAV------------NYQATSIVMSGI-QPHQ----NMALFRYLEDKINaeektawitnaitKGFTALEK 152
Cdd:PLN02473  83 TDLLGKTLEHRAIvdqwvevennyfYAVALPLVINLVfKPRLgepcDVALVEELKVKFD-------------KVLDVYEN 149

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 15226949  153 LLVScaGKYATGDEVYLADLFLAPQIHAAFNRFHIN--MEPFPTLARFYESYNELPAFQ 209
Cdd:PLN02473 150 RLAT--NRYLGGDEFTLADLTHMPGMRYIMNETSLSglVTSRENLNRWWNEISARPAWK 206

GST_N family, unknown subfamily 3; 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15226949  11 KLkLYSYwRSSCAHRVRIAL--TLKGLDYEYIPVNLLKGDQSDSDFkkiNPMGTVPALV-DGDVVINDSFAIIMYLD 84
Cdd:cd03049   2 KL-LYSP-TSPYVRKVRVAAheTGLGDDVELVLVNPWSDDESLLAV---NPLGKIPALVlDDGEALFDSRVICEYLD 73

glutathione dehydrogenase (ascorbate)

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15226949   22 CAHRVRIALTL--KGLDYEYIPVNLlkGDQSDSdFKKINPMGTVPALVDGDVVINDSFAIIMYLDDKYPEPPL 92
Cdd:PLN02817  73 CPFCQRVLLTLeeKHLPYDMKLVDL--TNKPEW-FLKISPEGKVPVVKLDEKWVADSDVITQALEEKYPDPPL 142

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949 111 MSGIQPHQNMA--LFRYLEDKIN-AEEKTAWITNAItkgFTALEKLLVScaGKYATGDEVYLADLFLAPQIhAAFNRFHI 187
Cdd:cd10291  13 MGGLGPMQGQAhhFKRYAPEKIPyAIKRYTNETKRL---YGVLDRRLAK--SKYLAGDEYSIADIAIWPWV-ARHEWQGI 86

                        90       100
                ....*....|....*....|..
gi 15226949 188 NMEPFPTLARFYESYNELPAFQ 209
Cdd:cd10291  87 DLADFPNLKRWFERLAARPAVQ 108

GST_N family, Omega-like subfamily; composed of uncharacterized proteins with similarity to class Omega 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. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. Like Omega enzymes, proteins in this subfamily contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226949  14 LYSYWRSSCAHRVRIALTLKGLDYEYIPVNLlkgDQSDSDFKKINPMGTVPALV-DGDVVINDSFAIIMY 82
Cdd:cd03060   3 LYSFRRCPYAMRARMALLLAGITVELREVEL---KNKPAEMLAASPKGTVPVLVlGNGTVIEESLDIMRW 69

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.

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gi 15226949  12 LKLYSYWRSSCAHRVRIALTLKGLDYEyIPVNLLKGDQSDSDFKKINPMGTVPALVDGD-VVINDSFAIIMYL 83
Cdd:cd03044   1 GTLYTYPGNPRSLKILAAAKYNGLDVE-IVDFQPGKENKTPEFLKKFPLGKVPAFEGADgFCLFESNAIAYYV 72

GST_N family, Class Mu subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The class Mu subfamily is composed of eukaryotic GSTs. In rats, at least six distinct class Mu subunits have been identified, with homologous genes in humans for five of these subunits. Class Mu GSTs can form homodimers and heterodimers, giving a large number of possible isoenzymes that can be formed, all with overlapping activities but different substrate specificities. They are the most abundant GSTs in human liver, skeletal muscle and brain, and are believed to provide protection against diseases including cancer and neurodegenerative disorders. Some isoenzymes have additional specific functions. Human GST M1-1 acts as an endogenous inhibitor of ASK1 (apoptosis signal-regulating kinase 1), thereby suppressing ASK1-mediated cell death. Human GSTM2-2 and 3-3 have been identified as prostaglandin E2 synthases in the brain and may play crucial roles in temperature and sleep-wake regulation.

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gi 15226949  17 YWR-SSCAHRVRIALTLKGLDYEyiPVNLLKGDQSDSD--------FKKINPMGTVPALVDGDVVINDSFAIIMYLDDKY 87
Cdd:cd03075   5 YWDiRGLAQPIRLLLEYTGEKYE--EKRYELGDAPDYDrsqwlnekFKLGLDFPNLPYYIDGDVKLTQSNAILRYIARKH 82