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 1958784663  58 VLYSYFRSSCSWRVRIALALKGIDYEIVPINLIKDGgQQFSEEFQTLNPMKQVPALKIDGITIGQSLAILEYLEETRPIP 137
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLLRDG-EQRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETYPDP 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958784663 138 RLLPQDPQKRAIVRMISDLIASGIQPLQNLSVLKQVGQ------ENQMPWAQKAITSGFN 191
Cdd:TIGR01262  80 PLLPADPIKRARVRALALLIACDIHPLNNLRVLQYLREklgveeEARNRWYQHWISKGFA 139

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 1958784663  58 VLYSYFRSSCSWRVRIALALKGIDYEIVPINLIKDGgQQFSEEFQTLNPMKQVPALKIDGITIGQSLAILEYLEETRPIP 137
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLLRDG-EQRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETYPDP 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958784663 138 RLLPQDPQKRAIVRMISDLIASGIQPLQNLSVLKQVGQ------ENQMPWAQKAITSGFN 191
Cdd:TIGR01262  80 PLLPADPIKRARVRALALLIACDIHPLNNLRVLQYLREklgveeEARNRWYQHWISKGFA 139

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958784663  59 LYSYFRSSCSWRVRIALALKGIDYEIVPINLIKdgGQQFSEEFQTLNPMKQVPALKIDGITIGQSLAILEYLEETRPIPR 138
Cdd:COG0625     4 LYGSPPSPNSRRVRIALEEKGLPYELVPVDLAK--GEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPEPP 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958784663 139 LLPQDPQKRAIVRMISDLIASGIQP--LQNLSVLKQVGQENQMPWAQKAITSGF 190
Cdd:COG0625    82 LLPADPAARARVRQWLAWADGDLHPalRNLLERLAPEKDPAAIARARAELARLL 135

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 1958784663  59 LYSYFRSSCSWRVRIALALKGIDYEIVPINLikDGGQQFSEEFQTLNPMKQVPALKIDGITIGQSLAILEYLEE 132
Cdd:pfam02798   5 LYGIRGSPRAHRIRWLLAEKGVEYEIVPLDF--GAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

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 1958784663  58 VLYSYFRSSCSWRVRIALALKGIDYEIVPINLIKDGgQQFSEEFQTLNPMKQVPALKIDGITIGQSLAILEYLEETRPIP 137
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLLRDG-EQRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETYPDP 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958784663 138 RLLPQDPQKRAIVRMISDLIASGIQPLQNLSVLKQVGQ------ENQMPWAQKAITSGFN 191
Cdd:TIGR01262  80 PLLPADPIKRARVRALALLIACDIHPLNNLRVLQYLREklgveeEARNRWYQHWISKGFA 139

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958784663  59 LYSYFRSSCSWRVRIALALKGIDYEIVPINLIKdgGQQFSEEFQTLNPMKQVPALKIDGITIGQSLAILEYLEETRPIPR 138
Cdd:COG0625     4 LYGSPPSPNSRRVRIALEEKGLPYELVPVDLAK--GEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPEPP 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958784663 139 LLPQDPQKRAIVRMISDLIASGIQP--LQNLSVLKQVGQENQMPWAQKAITSGF 190
Cdd:COG0625    82 LLPADPAARARVRQWLAWADGDLHPalRNLLERLAPEKDPAAIARARAELARLL 135

glutathione transferase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958784663  52 MQAGKPVLYS--YFRSSCSWRVRIALALKGIDYEIVPINLikDGGQQFSEEFQTLNPMKQVPALKIDGITIGQSLAILEY 129
Cdd:PRK15113    1 MSKPAITLYSdaHFFSPYVMSAFVALQEKGLPFELKTVDL--DAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEY 78

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1958784663 130 LEETRPIP---RLLPQDPQKRAIVRMI-----SDLIA 158
Cdd:PRK15113   79 LEERFAPPaweRIYPADLQARARARQIqawlrSDLMP 115

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 1958784663  59 LYSYFRSSCSWRVRIALALKGIDYEIVPINLIKdgGQQFSEEFQTLNPMKQVPALKIDGITIGQSLAILEYL 130
Cdd:cd03056     3 LYGFPLSGNCYKVRLLLALLGIPYEWVEVDILK--GETRTPEFLALNPNGEVPVLELDGRVLAESNAILVYL 72

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 1958784663  59 LYSYFRSSCSWRVRIALALKGIDYEIVPINLIKdgGQQFSEEFQTLNPMKQVPALKIDGITIGQSLAILEYLEE 132
Cdd:cd03053     4 LYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTK--GEHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAE 75

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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958784663 144 PQKRAIVRMISDLIASGIQPLQNLSVLKQVG------QENQMPWAQKAITSGFN 191
Cdd:cd03191     1 PKKRARVRAIALIIACDIHPLQNLRVLKYLTeklgvsEEEKLAWAQHWIERGFQ 54

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958784663  59 LYSyFRSSCSWRVRIALALKGIDYEIVPINLIKdgGQQFSEEFQTLNPMKQVPALkID----GITIGQSLAILEYLEET 133
Cdd:cd03048     4 LYT-HGTPNGFKVSIMLEELGLPYEIHPVDISK--GEQKKPEFLKINPNGRIPAI-VDhngtPLTVFESGAILLYLAEK 78

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 1958784663  59 LYsYFRSSCSWRVRIALALKGIDYEIVPINLikDGGQQFSEEFQTLNPMKQVPALKI-DGITIGQSLAILEYLEETRP 135
Cdd:cd03057     3 LY-YSPGACSLAPHIALEELGLPFELVRVDL--RTKTQKGADYLAINPKGQVPALVLdDGEVLTESAAILQYLADLHP 77

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 1958784663  58 VLYSYFRSSCSWRVRIALALKGIDYEIVPINLIKDggqqfSEEFQTLNPM-KQVPALKIDGITIGQSLAILEYLEET 133
Cdd:cd03058     2 KLLGAWASPFVLRVRIALALKGVPYEYVEEDLGNK-----SELLLASNPVhKKIPVLLHNGKPICESLIIVEYIDEA 73

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958784663  71 VRIALALKGIDYEIVPInlikDGGQQFSEEFQTLNPMKQVPALKIDGITIGQSLAILEYL 130
Cdd:cd03039    15 IRLLLADAGVEYEDVRI----TYEEWPELDLKPTLPFGQLPVLEIDGKKLTQSNAILRYL 70

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 1958784663  69 WRVRIALALKGIDYEIVPINL--IKDggqqfSEEFQTLNPMKQVPALK-IDGITIGQSLAILEYLEETRP 135
Cdd:cd03038    20 WKTRLALNHKGLEYKTVPVEFpdIPP-----ILGELTSGGFYTVPVIVdGSGEVIGDSFAIAEYLEEAYP 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 1958784663  67 CSW--RVRIALALKGIDYEIVPINLiKDGGQQFSEEfqtlNPMKQVPALKID-GITIGQSLAILEYLE 131
Cdd:cd03055    27 CPYaqRARLVLAAKNIPHEVININL-KDKPDWFLEK----NPQGKVPALEIDeGKVVYESLIICEYLD 89

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958784663  66 SCSWRVRIALALKGIDYEIVPINLIKdgGQQFSEEFQTLNPMKQVPALKIDGITIGQSLAILEYLEETRPI--PRLLPQD 143
Cdd:PLN02395   11 ASPKRALVTLIEKGVEFETVPVDLMK--GEHKQPEYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKYRSqgPDLLGKT 88

                          90       100
                  ....*....|....*....|....*..
gi 1958784663 144 PQKRAIVRMISDLIASGIQP-LQNLSV 169
Cdd:PLN02395   89 IEERGQVEQWLDVEATSYHPpLLNLTL 115

glutathionine S-transferase; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958784663  66 SCSWRVRIALALKGIDYEIVPINLIKDGGQQfSEEFQTLNPMKQVPALKID-GITIGQSLAILEYLEETRPIPRLLP 141
Cdd:PRK10542    9 ACSLASHITLRESGLDFTLVSVDLAKKRLEN-GDDYLAINPKGQVPALLLDdGTLLTEGVAIMQYLADSVPDRQLLA 84

putative S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958784663  73 IALALKGIDYEIVPINlIKDGgQQFSEEFQTLNPMKQVPALkID-----GITIGQSLAILEYLEETrpIPRLLPQDPQKR 147
Cdd:PRK11752   66 LALGVKGAEYDAWLIR-IGEG-DQFSSGFVEINPNSKIPAL-LDrsgnpPIRVFESGAILLYLAEK--FGAFLPKDLAAR 140

                  .
gi 1958784663 148 A 148
Cdd:PRK11752  141 T 141

NrdH-redoxin (NrdH) family; NrdH is a small monomeric protein with a conserved redox active CXXC motif within a TRX fold, characterized by a glutaredoxin (GRX)-like sequence and TRX-like activity profile. In vitro, it displays protein disulfide reductase activity that is dependent on TRX reductase, not glutathione (GSH). It is part of the NrdHIEF operon, where NrdEF codes for class Ib ribonucleotide reductase (RNR-Ib), an efficient enzyme at low oxygen levels. Under these conditions when GSH is mostly conjugated to spermidine, NrdH can still function and act as a hydrogen donor for RNR-Ib. It has been suggested that the NrdHEF system may be the oldest RNR reducing system, capable of functioning in a microaerophilic environment, where GSH was not yet available. NrdH from Corynebacterium ammoniagenes can form domain-swapped dimers, although it is unknown if this happens in vivo. Domain-swapped dimerization, which results in the blocking of the TRX reductase binding site, could be a mechanism for regulating the oxidation state of the protein.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958784663  58 VLYSyfRSSCSW--RVRIALALKGIDYEIVPInlikDGGQQFSEEFQTLNPMKQVPALKIDG 117
Cdd:cd02976     3 TVYT--KPDCPYckATKRFLDERGIPFEEVDV----DEDPEALEELKKLNGYRSVPVVVIGD 58

GST_N family, Class Alpha 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 Alpha subfamily is composed of eukaryotic GSTs which can form homodimer and heterodimers. There are at least six types of class Alpha GST subunits in rats, four of which have human counterparts, resulting in many possible isoenzymes with different activities, tissue distribution and substrate specificities. Human GSTA1-1 and GSTA2-2 show high GSH peroxidase activity. GSTA3-3 catalyzes the isomerization of intermediates in steroid hormone biosynthesis. GSTA4-4 preferentially catalyzes the GSH conjugation of alkenals.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958784663  56 KPVLYsYFRSSCSWR-VRIALALKGIDYEIVPI-------NLIKDGGQQFseefqtlnpmKQVPALKIDGITIGQSLAIL 127
Cdd:cd03077     1 KPVLH-YFNGRGRMEsIRWLLAAAGVEFEEKFIesaedleKLKKDGSLMF----------QQVPMVEIDGMKLVQTRAIL 69

                  ...
gi 1958784663 128 EYL 130
Cdd:cd03077    70 NYI 72

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958784663  57 PVLYSYFRSSCSWRVRIALALKGIDYEIVPINLiKDGgqqfSEEFQTLNPMKQVPAL-KIDGITIGQSLAIL 127
Cdd:cd03060     1 PILYSFRRCPYAMRARMALLLAGITVELREVEL-KNK----PAEMLAASPKGTVPVLvLGNGTVIEESLDIM 67

GST_N family, Class Pi 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 Pi GST is a homodimeric eukaryotic protein. The human GSTP1 is mainly found in erythrocytes, kidney, placenta and fetal liver. It is involved in stress responses and in cellular proliferation pathways as an inhibitor of JNK (c-Jun N-terminal kinase). Following oxidative stress, monomeric GSTP1 dissociates from JNK and dimerizes, losing its ability to bind JNK and causing an increase in JNK activity, thereby promoting apoptosis. GSTP1 is expressed in various tumors and is the predominant GST in a wide range of cancer cells. It has been implicated in the development of multidrug-resistant tumours.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958784663  71 VRIALALKGIDYEIVPInlikdGGQQFSEEFQTLNPMKQVPALKIDGITIGQSLAILEYL 130
Cdd:cd03076    16 IRLLLADQGISWEEERV-----TYEEWQESLKPKMLFGQLPCFKDGDLTLVQSNAILRHL 70