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 1695510488   2 KLYSFFNSSASYRVRIALALKGIDYQTVGVN-IRIGQQNALAYRRMNPVGLVPTLVtDDGESLGQSLAIVDWLDRHFPQT 80
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNlLRDGEQRSPEFLALNPQGLVPTLD-IDGEVLTQSLAIIEYLEETYPDP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1695510488  81 PLLPTSDPARSQALEIVYAIACDIHPINNMRVLRYLTDELKVSEEDKKRWYAHWIQQGLSAVEQLLRkSQSGRFCVGDAP 160
Cdd:TIGR01262  80 PLLPADPIKRARVRALALLIACDIHPLNNLRVLQYLREKLGVEEEARNRWYQHWISKGFAALEALLQ-PHAGRFCVGDTP 158

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1695510488 161 GLADCCLIPQWANALRMGCDLSGYPRCKAVYDACVQLPAFIAAAPENQQDKI 212
Cdd:TIGR01262 159 TLADLCLVPQVYNAERFGVDLTPYPTLRRIAAALAALPAFQRAHPENQPDTP 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 1695510488   2 KLYSFFNSSASYRVRIALALKGIDYQTVGVN-IRIGQQNALAYRRMNPVGLVPTLVtDDGESLGQSLAIVDWLDRHFPQT 80
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNlLRDGEQRSPEFLALNPQGLVPTLD-IDGEVLTQSLAIIEYLEETYPDP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1695510488  81 PLLPTSDPARSQALEIVYAIACDIHPINNMRVLRYLTDELKVSEEDKKRWYAHWIQQGLSAVEQLLRkSQSGRFCVGDAP 160
Cdd:TIGR01262  80 PLLPADPIKRARVRALALLIACDIHPLNNLRVLQYLREKLGVEEEARNRWYQHWISKGFAALEALLQ-PHAGRFCVGDTP 158

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1695510488 161 GLADCCLIPQWANALRMGCDLSGYPRCKAVYDACVQLPAFIAAAPENQQDKI 212
Cdd:TIGR01262 159 TLADLCLVPQVYNAERFGVDLTPYPTLRRIAAALAALPAFQRAHPENQPDTP 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 1695510488  89 ARSQALEIVYAIACDIHPINNMRVLRYLTDELKVSEEDKKRWYAHWIQQGLSAVEQLLrKSQSGRFCVGDAPGLADCCLI 168
Cdd:cd03191     3 KRARVRAIALIIACDIHPLQNLRVLKYLTEKLGVSEEEKLAWAQHWIERGFQALEKLL-ASTAGKYCVGDEPTLADICLV 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1695510488 169 PQWANALRMGCDLSGYPRCKAVYDACVQLPAFIAAAPENQ 208
Cdd:cd03191    82 PQVYNARRFGVDLSPYPTIVRINEACLELPAFQAAHPENQ 121

glutathionine S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1695510488   1 MKLysFFNSSA-SYRVRIALALKGIDYQTVGVNIRIGQ-QNALAYRRMNPVGLVPTLVTDDGESLGQSLAIVDWL----- 73
Cdd:PRK10542    1 MKL--FYKPGAcSLASHITLRESGLDFTLVSVDLAKKRlENGDDYLAINPKGQVPALLLDDGTLLTEGVAIMQYLadsvp 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1695510488  74 DRHFpqtpLLPTSDPARSQALEIVYAIACDIH----PINNMRVlrylTDELKVSEEDKkrwyahwIQQGLSAVEQLLRKS 149
Cdd:PRK10542   79 DRQL----LAPVGSLSRYHTIEWLNYIATELHkgftPLFRPDT----PEEYKPTVRAQ-------LEKKFQYVDEALADE 143

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1695510488 150 Q---SGRFCVGDAPGLAdcclIPQWANALRMgcDLSGYPRCKAVYDACVQLPAFIAA 203
Cdd:PRK10542  144 QwicGQRFTIADAYLFT----VLRWAYAVKL--NLEGLEHIAAYMQRVAERPAVAAA 194

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 1695510488   2 KLYSFFNSSASYRVRIALALKGIDYQTVGVN-IRIGQQNALAYRRMNPVGLVPTLVtDDGESLGQSLAIVDWLDRHFPQT 80
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNlLRDGEQRSPEFLALNPQGLVPTLD-IDGEVLTQSLAIIEYLEETYPDP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1695510488  81 PLLPTSDPARSQALEIVYAIACDIHPINNMRVLRYLTDELKVSEEDKKRWYAHWIQQGLSAVEQLLRkSQSGRFCVGDAP 160
Cdd:TIGR01262  80 PLLPADPIKRARVRALALLIACDIHPLNNLRVLQYLREKLGVEEEARNRWYQHWISKGFAALEALLQ-PHAGRFCVGDTP 158

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1695510488 161 GLADCCLIPQWANALRMGCDLSGYPRCKAVYDACVQLPAFIAAAPENQQDKI 212
Cdd:TIGR01262 159 TLADLCLVPQVYNAERFGVDLTPYPTLRRIAAALAALPAFQRAHPENQPDTP 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 1695510488  89 ARSQALEIVYAIACDIHPINNMRVLRYLTDELKVSEEDKKRWYAHWIQQGLSAVEQLLrKSQSGRFCVGDAPGLADCCLI 168
Cdd:cd03191     3 KRARVRAIALIIACDIHPLQNLRVLKYLTEKLGVSEEEKLAWAQHWIERGFQALEKLL-ASTAGKYCVGDEPTLADICLV 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1695510488 169 PQWANALRMGCDLSGYPRCKAVYDACVQLPAFIAAAPENQ 208
Cdd:cd03191    82 PQVYNARRFGVDLSPYPTIVRINEACLELPAFQAAHPENQ 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 1695510488   1 MKLYSFFNSSASYRVRIALALKGIDYQTVGVNIRIGQQnaLAYRRMNPVGLVPTLVtDDGESLGQSLAIVDWLD 74
Cdd:cd00570     1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQ--EEFLALNPLGKVPVLE-DGGLVLTESLAILEYLA 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 1695510488   1 MKLYSFFNSSASYRVRIALALKGIDYQTVGVNIRIGQQNALAYRRMNPVGLVPTLVtDDGESLGQSLAIVDWL 73
Cdd:cd03056     1 MKLYGFPLSGNCYKVRLLLALLGIPYEWVEVDILKGETRTPEFLALNPNGEVPVLE-LDGRVLAESNAILVYL 72

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1695510488   3 LYSFFNSSASYRVRIALALKGIDYQTVGVNiriGQQNALAYRRMNPVGLVPTLVtDDGESLGQSLAIVDWLDRHFPQTP 81
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIP---PGDHPPELLAKNPLGKVPVLE-DDGGILCESLAIIDYLEELYPGPP 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 1695510488   1 MKLYSFFNSSASYRVRIALALKGIDYQTVGVNIRIGQQNALAYRRMNPVGLVPTLVtDDGESLGQSLAIVDWLDR 75
Cdd:pfam02798   3 LTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALE-DGGKKLTESRAILEYIAR 76

stringent starvation protein A; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1695510488   1 MKLYSFFNSSASYRVRIALALKGidyqtVGVNIRIGQQNAL--AYRRMNPVGLVPTLVtdDGE-SLGQSLAIVDWLDRHF 77
Cdd:PRK09481   11 MTLFSGPTDIYSHQVRIVLAEKG-----VSVEIEQVEKDNLpqDLIDLNPYQSVPTLV--DRElTLYESRIIMEYLDERF 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1695510488  78 PQTPLLPTSDPARSQALEIVYAIACDIHPINNmRVLRYLTDElkvSEEDKKRwyahwIQQGLSAVEQLLRKSQsgrFCVG 157
Cdd:PRK09481   84 PHPPLMPVYPVARGESRLMMHRIEKDWYSLMN-KIVNGSASE---ADAARKQ-----LREELLAIAPVFGEKP---YFMS 151

                         170       180
                  ....*....|....*....|....*.
gi 1695510488 158 DAPGLADCCLIPQWANALRMGCDLSG 183
Cdd:PRK09481  152 EEFSLVDCYLAPLLWRLPVLGIELSG 177

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 1695510488   1 MKLYSFFNSSASYRVRIALALKGIDYQTVGVNIRIGQQNALAYRRMNPVGLVPTLVtDDGESLGQSLAIVDWLDR 75
Cdd:cd03053     2 LKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALE-DGDLKLFESRAITRYLAE 75

putative glutathione S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1695510488   1 MKLYSFFNSSASYRVRIALALKGIDYQTVgvnirigqqNALAYR------RMNPVGLVPTLVTDDGESLGQSLAIVDWLD 74
Cdd:PRK10357    1 MKLIGSYTSPFVRKISILLLEKGITFEFV---------NELPYNadngvaQYNPLGKVPALVTEEGECWFDSPIIAEYIE 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1695510488  75 RHFPQTPLLPtSDPARSQALEIVYAIACDIHPINNMRVLRYLTDELKVSEEDKKRWYAHwIQQGLSAVEQLLRKSQSGrf 154
Cdd:PRK10357   72 LLNVAPAMLP-RDPLAALRVRQLEALADGIMDAALVSVREQARPAAQQSEDELLRQREK-INRSLDALEGYLVDGTLK-- 147

                         170
                  ....*....|....*..
gi 1695510488 155 cvGDAPGLAD----CCL 167
Cdd:PRK10357  148 --TDTVNLATiaiaCAV 162

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 1695510488   1 MKLYSFFNSSASYRVRIALALKGIDYQTVGVNIRIGQQNALayrRMNPV-GLVPTLVTdDGESLGQSLAIVDWLD 74
Cdd:cd03058     1 VKLLGAWASPFVLRVRIALALKGVPYEYVEEDLGNKSELLL---ASNPVhKKIPVLLH-NGKPICESLIIVEYID 71

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1695510488   1 MKLYSFFNSSASYRVRIALALKGIDYQTVGVNirigQQNA---LAyrRMNPVGLVPTLVTDDgESLGQSLAIVDWLDRHF 77
Cdd:cd03059     1 MTLYSGPDDVYSHRVRIVLAEKGVSVEIIDVD----PDNPpedLA--ELNPYGTVPTLVDRD-LVLYESRIIMEYLDERF 73

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1695510488  10 SASYRVRIALALKGIDYQTVGVNIRIGQQNALAYRRMNPVGLVPTLVtdDGE-SLGQSLAIVDWL-DRHFPQTP-LLPTS 86
Cdd:PLN02395   11 ASPKRALVTLIEKGVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIV--DGDyKIFESRAIMRYYaEKYRSQGPdLLGKT 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1695510488  87 DPARSQALEIVYAIACDIHP-INNM-------RVLRYLTDELKVSEEDKKrwyahwIQQGLSAVEQLLRKSqsgRFCVGD 158
Cdd:PLN02395   89 IEERGQVEQWLDVEATSYHPpLLNLtlhilfaSKMGFPADEKVIKESEEK------LAKVLDVYEARLSKS---KYLAGD 159

                         170
                  ....*....|.
gi 1695510488 159 APGLADCCLIP 169
Cdd:PLN02395  160 FVSLADLAHLP 170

GST_N family, Gamma subunit of Elongation Factor 1B (EFB1gamma) subfamily; EF1Bgamma is part of the eukaryotic translation elongation factor-1 (EF1) complex which plays a central role in the elongation cycle during protein biosynthesis. EF1 consists of two functionally distinct units, EF1A and EF1B. EF1A catalyzes the GTP-dependent binding of aminoacyl-tRNA to the ribosomal A site concomitant with the hydrolysis of GTP. The resulting inactive EF1A:GDP complex is recycled to the active GTP form by the guanine-nucleotide exchange factor EF1B, a complex composed of at least two subunits, alpha and gamma. Metazoan EFB1 contain a third subunit, beta. The EF1B gamma subunit contains a GST fold consisting of an N-terminal TRX-fold domain and a C-terminal alpha helical domain. The GST-like domain of EF1Bgamma is believed to mediate the dimerization of the EF1 complex, which in yeast is a dimer of the heterotrimer EF1A:EF1Balpha:EF1Bgamma. In addition to its role in protein biosynthesis, EF1Bgamma may also display other functions. The recombinant rice protein has been shown to possess GSH conjugating activity. The yeast EF1Bgamma binds membranes in a calcium dependent manner and is also part of a complex that binds to the msrA (methionine sulfoxide reductase) promoter suggesting a function in the regulation of its gene expression.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1695510488   2 KLYSFFNSSASYRVRIALALKGIDyqtvgVNIRIGQQNAL----AYRRMNPVGLVPTLVTDDGESLGQSLAIV 70
Cdd:cd03044     2 TLYTYPGNPRSLKILAAAKYNGLD-----VEIVDFQPGKEnktpEFLKKFPLGKVPAFEGADGFCLFESNAIA 69

GST_N family, Glutaredoxin 2 (GRX2) subfamily; composed of bacterial proteins similar to E. coli GRX2, an atypical GRX with a molecular mass of about 24kD, compared with other GRXs which are 9-12kD in size. GRX2 adopts a GST fold containing an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. It contains a redox active CXXC motif located in the N-terminal domain but is not able to reduce ribonucleotide reductase like other GRXs. However, it catalyzes GSH-dependent protein disulfide reduction of other substrates efficiently. GRX2 is thought to function primarily in catalyzing the reversible glutathionylation of proteins in cellular redox regulation including stress responses.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1695510488   1 MKLYSFFNSSASYRVRIALALKGIDYQTvgvnIRIGQQNALAYRRMNPVGLVPTLVTDDGESLGQSLAIVDWLDR 75
Cdd:cd03037     1 MKLYIYEHCPFCVKARMIAGLKNIPVEQ----IILQNDDEATPIRMIGAKQVPILEKDDGSFMAESLDIVAFIDE 71

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1695510488   1 MKLYSFFNSSASYRVRIALALKGIDYQTVGVNIRIGQQNALAYRRMNPVGLVPTLVtDDGESLGQSLAIVDWL 73
Cdd:cd03045     1 IDLYYLPGSPPCRAVLLTAKALGLELNLKEVNLMKGEHLKPEFLKLNPQHTVPTLV-DNGFVLWESHAILIYL 72

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1695510488   1 MKLYSFFNSSASYRVRIALALKGIDYQTVGVNIRIGQQNALAYRRMNPVGLVPTLVtDDGESLGQSLAIVDWL 73
Cdd:cd03047     1 LTIWGRRSSINVQKVLWLLDELGLPYERIDAGGQFGGLDTPEFLAMNPNGRVPVLE-DGDFVLWESNAILRYL 72

Glutathione S-transferase, C-terminal domain; GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins in E. coli are also included in the alignment but are not known to have GST activity. The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain. In plants, GSTs are encoded by a large gene family (48 GST genes in Arabidopsis) and can be divided into the phi, tau, theta, zeta, and lambda classes.

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gi 1695510488 139 LSAVEQLLRKSqsgRFCVGDAPGLADCCLIP--QWANALRMGCDLSGYPRCKAVYDACVQLP 198
Cdd:pfam00043  35 LSALEEVLKGQ---TYLVGDKLTLADIALAPalLWLYELDPACLREKFPNLKAWFERVAARP 93

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 1695510488   3 LYSFFNSSASYRVRIALALKGIDYQTVGVNIRIGQQNALAYRRMNPVGLVPTLVTDDgESLGQSLAIVDWLD 74
Cdd:cd03052     3 LYHWTQSFSSQKVRLVIAEKGLRCEEYDVSLPLSEHNEPWFMRLNPTGEVPVLIHGD-NIICDPTQIIDYLE 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.

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gi 1695510488  15 VRIALALKGIDYQtvgvNIRI--GQQNALAYRRMNPVGLVPTLVtDDGESLGQSLAIVDWL 73
Cdd:cd03039    15 IRLLLADAGVEYE----DVRItyEEWPELDLKPTLPFGQLPVLE-IDGKKLTQSNAILRYL 70

C-terminal, alpha helical domain of an unknown subfamily 5 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 5; 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 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.

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gi 1695510488 139 LSAVEQLLRKSqsgRFCVGDAPGLADCCLIP---QWANALRMGCDLSGYPRCKAVYDACVQLPAFIAA 203
Cdd:cd03196    50 LAELEARLSQH---AYLFGDRPSLADYAIFPfvrQFAHVDRDWFDASPYPNLRRWLNRFLQSPLFSKI 114