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 974006197    2 QLHSFFNSSTSYRVRIALALKGLPFDVVPVNL-RKQEQRAADYVARNPSAGVPLLTDGDFQLSQSLAIIDYLDATHPEPR 80
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLlRDGEQRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETYPDPP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974006197   81 LIPAAPRERARVLELSNAIACDIHPVNNMRILRYLQEELGATDAQKNAWYHHWIREGLTAVETLLaRHGGGAYCLGDAPT 160
Cdd:TIGR01262  81 LLPADPIKRARVRALALLIACDIHPLNNLRVLQYLREKLGVEEEARNRWYQHWISKGFAALEALL-QPHAGRFCVGDTPT 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 974006197  161 LADCCVVPQVANAQRMGCDLSAYPRLVGVYEHCLAQPAFQQAAPANQPDYI 211
Cdd:TIGR01262 160 LADLCLVPQVYNAERFGVDLTPYPTLRRIAAALAALPAFQRAHPENQPDTP 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 974006197    2 QLHSFFNSSTSYRVRIALALKGLPFDVVPVNL-RKQEQRAADYVARNPSAGVPLLTDGDFQLSQSLAIIDYLDATHPEPR 80
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLlRDGEQRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETYPDPP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974006197   81 LIPAAPRERARVLELSNAIACDIHPVNNMRILRYLQEELGATDAQKNAWYHHWIREGLTAVETLLaRHGGGAYCLGDAPT 160
Cdd:TIGR01262  81 LLPADPIKRARVRALALLIACDIHPLNNLRVLQYLREKLGVEEEARNRWYQHWISKGFAALEALL-QPHAGRFCVGDTPT 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 974006197  161 LADCCVVPQVANAQRMGCDLSAYPRLVGVYEHCLAQPAFQQAAPANQPDYI 211
Cdd:TIGR01262 160 LADLCLVPQVYNAERFGVDLTPYPTLRRIAAALAALPAFQRAHPENQPDTP 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 974006197  86 PRERARVLELSNAIACDIHPVNNMRILRYLQEELGATDAQKNAWYHHWIREGLTAVETLLARHgGGAYCLGDAPTLADCC 165
Cdd:cd03191    1 PKKRARVRAIALIIACDIHPLQNLRVLKYLTEKLGVSEEEKLAWAQHWIERGFQALEKLLAST-AGKYCVGDEPTLADIC 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 974006197 166 VVPQVANAQRMGCDLSAYPRLVGVYEHCLAQPAFQQAAPANQ 207
Cdd:cd03191   80 LVPQVYNARRFGVDLSPYPTIVRINEACLELPAFQAAHPENQ 121

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 974006197    1 MQLHSFFNSSTSYRVRIALALKGLPFDVVPVNLRKQEQRAADYVARNPSAGVPLLTDGDFQLSQSLAIIDYLD 73
Cdd:pfam02798   3 LTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIA 75

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 974006197    2 QLHSFFNSSTSYRVRIALALKGLPFDVVPVNL-RKQEQRAADYVARNPSAGVPLLTDGDFQLSQSLAIIDYLDATHPEPR 80
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLlRDGEQRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETYPDPP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974006197   81 LIPAAPRERARVLELSNAIACDIHPVNNMRILRYLQEELGATDAQKNAWYHHWIREGLTAVETLLaRHGGGAYCLGDAPT 160
Cdd:TIGR01262  81 LLPADPIKRARVRALALLIACDIHPLNNLRVLQYLREKLGVEEEARNRWYQHWISKGFAALEALL-QPHAGRFCVGDTPT 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 974006197  161 LADCCVVPQVANAQRMGCDLSAYPRLVGVYEHCLAQPAFQQAAPANQPDYI 211
Cdd:TIGR01262 160 LADLCLVPQVYNAERFGVDLTPYPTLRRIAAALAALPAFQRAHPENQPDTP 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 974006197  86 PRERARVLELSNAIACDIHPVNNMRILRYLQEELGATDAQKNAWYHHWIREGLTAVETLLARHgGGAYCLGDAPTLADCC 165
Cdd:cd03191    1 PKKRARVRAIALIIACDIHPLQNLRVLKYLTEKLGVSEEEKLAWAQHWIERGFQALEKLLAST-AGKYCVGDEPTLADIC 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 974006197 166 VVPQVANAQRMGCDLSAYPRLVGVYEHCLAQPAFQQAAPANQ 207
Cdd:cd03191   80 LVPQVYNARRFGVDLSPYPTIVRINEACLELPAFQAAHPENQ 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 974006197   1 MQLHSFFNSSTSYRVRIALALKGLPFDVVPVNLRKQEQRaaDYVARNPSAGVPLLTDGDFQLSQSLAIIDYLD 73
Cdd:cd00570    1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQE--EFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

GST_N family, unknown subfamily 4; 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 974006197   1 MQLHSFFNSSTSYRVRIALALKGLPFDVVPVNLRKQEQRAADYVARNPSAGVPLLTDGDFQLSQSLAIIDYL 72
Cdd:cd03056    1 MKLYGFPLSGNCYKVRLLLALLGIPYEWVEVDILKGETRTPEFLALNPNGEVPVLELDGRVLAESNAILVYL 72

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 974006197   1 MQLHSFfNSSTSYRVRIALALKGLPFDVVPVNLRKQEQRAADYVARNPSAGVPLLTDGDFQLSQSLAIIDYLDATHP 77
Cdd:cd03046    1 ITLYHL-PRSRSFRILWLLEELGLPYELVLYDRGPGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEKYG 76

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974006197    3 LHSFFNSSTSYRVRIALALKGLPFDVVPVNLrkqEQRAADYVARNPSAGVPLLTDGDFQLSQSLAIIDYLDATHPEPR 80
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIPP---GDHPPELLAKNPLGKVPVLEDDGGILCESLAIIDYLEELYPGPP 75

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974006197    9 SSTSYRVRIALALKGLPFDVVPVNLrKQEQRAADYVARNPSAGVP-LLTDGDFQLSQSLAIIDYLDAT 75
Cdd:pfam13409   2 SPFSHRVRLALEEKGLPYEIELVDL-DPKDKPPELLALNPLGTVPvLVLPDGTVLTDSLVILEYLEEL 68

stringent starvation protein A; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974006197   1 MQLHSFFNSSTSYRVRIALALKGLPFDVVPVNLRKQEQraaDYVARNPSAGVPLLTDGDFQLSQSLAIIDYLDATHPEPR 80
Cdd:PRK09481  11 MTLFSGPTDIYSHQVRIVLAEKGVSVEIEQVEKDNLPQ---DLIDLNPYQSVPTLVDRELTLYESRIIMEYLDERFPHPP 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974006197  81 LIPAAPRERARVLELSNAIACDIHPVNNmRILRYLQEELGATDAQknawyhhwIREGLTAVETLLARHgggAYCLGDAPT 160
Cdd:PRK09481  88 LMPVYPVARGESRLMMHRIEKDWYSLMN-KIVNGSASEADAARKQ--------LREELLAIAPVFGEK---PYFMSEEFS 155

                        170       180
                 ....*....|....*....|.
gi 974006197 161 LADCCVVPQVANAQRMGCDLS 181
Cdd:PRK09481 156 LVDCYLAPLLWRLPVLGIELS 176

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974006197  10 STSYRVRIALALKGLPFDVVPVNLRKQEQRAADYVARNPSAGVPLLTDGDFQLSQSLAIIDYLDATHPE--PRLIPAAPR 87
Cdd:PLN02395  11 ASPKRALVTLIEKGVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKYRSqgPDLLGKTIE 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974006197  88 ERARVLELSNAIACDIHP-VNNMRILRYLQEELGATDAQKnawyhhWIREGLTAVETLL----ARHGGGAYCLGDAPTLA 162
Cdd:PLN02395  91 ERGQVEQWLDVEATSYHPpLLNLTLHILFASKMGFPADEK------VIKESEEKLAKVLdvyeARLSKSKYLAGDFVSLA 164

                 ....*.
gi 974006197 163 DCCVVP 168
Cdd:PLN02395 165 DLAHLP 170

GST_N family, Class Tau 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 plant-specific class Tau GST subfamily has undergone extensive gene duplication. The Arabidopsis and Oryza genomes contain 28 and 40 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Phi GSTs, showing class specificity in substrate preference. Tau enzymes are highly efficient in detoxifying diphenylether and aryloxyphenoxypropionate herbicides. In addition, Tau GSTs play important roles in intracellular signalling, biosynthesis of anthocyanin, responses to soil stresses and responses to auxin and cytokinin hormones.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 974006197   1 MQLHSFFNSSTSYRVRIALALKGLPFDVVPVNLRKQEQRaadYVARNPSAG-VPLLTDGDFQLSQSLAIIDYLDAT 75
Cdd:cd03058    1 VKLLGAWASPFVLRVRIALALKGVPYEYVEEDLGNKSEL---LLASNPVHKkIPVLLHNGKPICESLIIVEYIDEA 73

glutathionine S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974006197  17 IALALKGLPFDVVPVNLR-KQEQRAADYVARNPSAGVP-LLTDGDFQLSQSLAIIDYLDATHPEPRLI-PAAPRERARVL 93
Cdd:PRK10542  16 ITLRESGLDFTLVSVDLAkKRLENGDDYLAINPKGQVPaLLLDDGTLLTEGVAIMQYLADSVPDRQLLaPVGSLSRYHTI 95

                         90
                 ....*....|.
gi 974006197  94 ELSNAIACDIH 104
Cdd:PRK10542  96 EWLNYIATELH 106

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 974006197  15 VRIALALKGLPFDVVPVNLRKQEQRAADYVARNPSAGVPLLTDGDFQLSQSLAIIDYL 72
Cdd:cd03045   15 VLLTAKALGLELNLKEVNLMKGEHLKPEFLKLNPQHTVPTLVDNGFVLWESHAILIYL 72

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 974006197   1 MQLHSFFNSSTSYRVRIALALKGLPFDVVPVNLrkqEQRAADYVARNPSAGVPLLTDGDFQLSQSLAIIDYLD 73
Cdd:cd03059    1 MTLYSGPDDVYSHRVRIVLAEKGVSVEIIDVDP---DNPPEDLAELNPYGTVPTLVDRDLVLYESRIIMEYLD 70

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 974006197  87 RERARVLELSNAIACDIHPvnNMRILRYLQEELGATDAQKnawYHHWIREGLTAVETLLARH-GGGAYCLGDAPTLADC- 164
Cdd:cd03188    1 LERARLLEWLNFIASELHK--AFGPLFYPARWADDALAEE---VKAAARERLERRLAYLDAQlAGGPYLLGDQFSVADAy 75

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 974006197 165 CVVpqVAN-AQRMGCDLSAYPRLVGVYEHCLAQPAFQQA 202
Cdd:cd03188   76 LFV--VLRwARAVGLDLSDWPHLAAYLARVAARPAVQAA 112

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 974006197   9 SSTSYRVRIALALKGLPFDVVPVNLrKQEQRAADYVARNPSAGVPLLTDGD-FQLSQSLAIIDYLDATHP 77
Cdd:cd03038   16 SPNVWKTRLALNHKGLEYKTVPVEF-PDIPPILGELTSGGFYTVPVIVDGSgEVIGDSFAIAEYLEEAYP 84

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 974006197  14 RVRIALALKGLPFDVVPVNL-RKQEQraadYVARNPSAGVPLL-TDGDFQLSQSLAIIDYLD 73
Cdd:cd03055   32 RARLVLAAKNIPHEVININLkDKPDW----FLEKNPQGKVPALeIDEGKVVYESLIICEYLD 89

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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 members include the class II insect GSTs, S-crystallins from cephalopods 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. Also members are novel GSTs from the fungus Cunninghamella elegans, designated as class Gamma, and from the protozoan Blepharisma japonicum, described as a light-inducible GST.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 974006197  15 VRIALALKGLPFDVVPVNlrKQEQRAADYVARNPSAGVPLLTDGDFQLSQSLAIIDYL 72
Cdd:cd03039   15 IRLLLADAGVEYEDVRIT--YEEWPELDLKPTLPFGQLPVLEIDGKKLTQSNAILRYL 70

GST_N family, Ganglioside-induced differentiation-associated protein 1 (GDAP1) subfamily; GDAP1 was originally identified as a highly expressed gene at the differentiated stage of GD3 synthase-transfected cells. More recently, mutations in GDAP1 have been reported to cause both axonal and demyelinating autosomal-recessive Charcot-Marie-Tooth (CMT) type 4A neuropathy. CMT is characterized by slow and progressive weakness and atrophy of muscles. Sequence analysis of GDAP1 shows similarities and differences with GSTs; it appears to contain both N-terminal TRX-fold and C-terminal alpha helical domains of GSTs, however, it also contains additional C-terminal transmembrane domains unlike GSTs. GDAP1 is mainly expressed in neuronal cells and is localized in the mitochondria through its transmembrane domains. It does not exhibit GST activity using standard substrates.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 974006197   3 LHSFFNSSTSYRVRIALALKGLPFDVVPVNLRKQEQRAADYVARNPSAGVPLLTDGDFQLSQSLAIIDYLD 73
Cdd:cd03052    3 LYHWTQSFSSQKVRLVIAEKGLRCEEYDVSLPLSEHNEPWFMRLNPTGEVPVLIHGDNIICDPTQIIDYLE 73

C-terminal, alpha helical domain of Metaxin and related proteins; Glutathione S-transferase (GST) C-terminal domain 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. Other members are the cadmium-inducible lysosomal protein CDR-1 and its homologs from C. elegans, and the failed axon connections (fax) protein from Drosophila. CDR-1 is an integral membrane protein that functions to protect against cadmium toxicity and may also have a role in osmoregulation to maintain salt balance in C. elegans. The fax gene of Drosophila was identified as a genetic modifier of Abelson (Abl) tyrosine kinase. The fax protein is localized in cellular membranes and is expressed in embryonic mesoderm and axons of the central nervous system.

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gi 974006197 135 REGLTAVETLLarhGGGAYCLGDAPTLADCCVVPQVANAQRMGCDLSAYPRLVGVY----EHC 193
Cdd:cd03193   25 LEDLEALSTLL---GDKKFLFGDKPTSVDATVFAHLASILYPPEDSPLLRVLVASSpnlvEYC 84

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

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gi 974006197  138 LTAVETLLARHGGGaYCLGDAPTLAD---CCVVPQVANAQRMGCdLSAYPRLVGVYEHCLAQP 197
Cdd:pfam14497  35 LGYFEKVLNKNGGG-YLVGDKLTYADlalFQVLDGLLYPKAPDA-LDKYPKLKALHERVAARP 95

C-terminal, alpha helical domain of Class Sigma-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Sigma_like; composed of GSTs belonging to class Sigma and similar proteins, including GSTs from class Mu, Pi, and Alpha. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. Vertebrate class Sigma GSTs are characterized as GSH-dependent hematopoietic prostaglandin (PG) D synthases and are responsible for the production of PGD2 by catalyzing the isomerization of PGH2. The functions of PGD2 include the maintenance of body temperature, inhibition of platelet aggregation, bronchoconstriction, vasodilation, and mediation of allergy and inflammation. Other class Sigma-like members include the class II insect GSTs, S-crystallins from cephalopods, nematode-specific GSTs, and 28-kDa GSTs from parasitic flatworms. Drosophila GST2 is associated with indirect flight muscle and exhibits preference for catalyzing GSH conjugation to lipid peroxidation products, indicating an anti-oxidant role. S-crystallin constitutes the major lens protein in cephalopod eyes and is responsible for lens transparency and proper refractive index. The 28-kDa GST from Schistosoma is a multifunctional enzyme, exhibiting GSH transferase, GSH peroxidase, and PGD2 synthase activities, and may play an important role in host-parasite interactions. Members also include novel GSTs from the fungus Cunninghamella elegans, designated as class Gamma, and from the protozoan Blepharisma japonicum, described as a light-inducible GST.

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gi 974006197  88 ERARVLELSNAIAcDIHpvnnMRILRYLQEELGATDAQKNAW-----YHHWiregLTAVETLLARHGGGaYCLGDAPTLA 162
Cdd:cd03192    2 EEARVDAIVDTIA-DLR----AEFAPYFYEPDGEEKKEKKKEfleeaLPKF----LGKFEKILKKSGGG-YFVGDKLTWA 71

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gi 974006197 163 D---CCVVPQVANAQRMgCDLSAYPRLVGVYEH 192
Cdd:cd03192   72 DlalFDVLDYLLYLLPK-DLLEKYPKLKALRER 103

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 974006197   3 LHSFFNSSTSYRVRIALALKGLPFDVVPVNLRkqeQRAADYVARNPSAGVP-LLTDGDFQLSQSLAII 69
Cdd:cd03060    3 LYSFRRCPYAMRARMALLLAGITVELREVELK---NKPAEMLAASPKGTVPvLVLGNGTVIEESLDIM 67