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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045   1 MKVYELRRAPNARRVRMFLAEKGIEMEYQQVDLGAGENLAPAFLTKNPAGRIPVLElDDGTCLSETLAICRYFEELHPEP 80
Cdd:COG0625     2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLV-DDGLVLTESLAILEYLAERYPEP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045  81 NLFGSTALERATIEMWSRFIEFNLWLPTGMAFRHItgfykdRERVFPEWGEECKQQAQIWFDKLDARLAEVPYIAGERFT 160
Cdd:COG0625    81 PLLPADPAARARVRQWLAWADGDLHPALRNLLERL------APEKDPAAIARARAELARLLAVLEARLAGGPYLAGDRFS 154

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1430951045 161 IADILAFCTIDFGKVVGLRItPEQPHLQDWHDRVSARSSAQA 202
Cdd:COG0625   155 IADIALAPVLRRLDRLGLDL-ADYPNLAAWLARLAARPAFQR 195

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045   1 MKVYELRRAPNARRVRMFLAEKGIEMEYQQVDLGAGENLAPAFLTKNPAGRIPVLElDDGTCLSETLAICRYFEELHPEP 80
Cdd:COG0625     2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLV-DDGLVLTESLAILEYLAERYPEP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045  81 NLFGSTALERATIEMWSRFIEFNLWLPTGMAFRHItgfykdRERVFPEWGEECKQQAQIWFDKLDARLAEVPYIAGERFT 160
Cdd:COG0625    81 PLLPADPAARARVRQWLAWADGDLHPALRNLLERL------APEKDPAAIARARAELARLLAVLEARLAGGPYLAGDRFS 154

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1430951045 161 IADILAFCTIDFGKVVGLRItPEQPHLQDWHDRVSARSSAQA 202
Cdd:COG0625   155 IADIALAPVLRRLDRLGLDL-ADYPNLAAWLARLAARPAFQR 195

glutathionine S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045  19 LAEKGIEMEYQQVDLGA-----GENlapaFLTKNPAGRIPVLELDDGTCLSETLAICRYFEELHPEPNLFGST-ALER-A 91
Cdd:PRK10542   18 LRESGLDFTLVSVDLAKkrlenGDD----YLAINPKGQVPALLLDDGTLLTEGVAIMQYLADSVPDRQLLAPVgSLSRyH 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045  92 TIEmWSRFIEFNLWLPTGMAFRhitgfykdrervfPEWGEECK----QQAQIWFDKLDARLAEVPYIAGERFTIADILAF 167
Cdd:PRK10542   94 TIE-WLNYIATELHKGFTPLFR-------------PDTPEEYKptvrAQLEKKFQYVDEALADEQWICGQRFTIADAYLF 159

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1430951045 168 CTIDFGKVVGLRITpEQPHLQDWHDRVSARSSAQA 202
Cdd:PRK10542  160 TVLRWAYAVKLNLE-GLEHIAAYMQRVAERPAVAA 193

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045   1 MKVYELRRAPNARRVRMFLAEKGIEMEYQQVDLGAGENLAPAFLTKNPAGRIPVLElDDGTCLSETLAICRYFEELHPEP 80
Cdd:COG0625     2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLV-DDGLVLTESLAILEYLAERYPEP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045  81 NLFGSTALERATIEMWSRFIEFNLWLPTGMAFRHItgfykdRERVFPEWGEECKQQAQIWFDKLDARLAEVPYIAGERFT 160
Cdd:COG0625    81 PLLPADPAARARVRQWLAWADGDLHPALRNLLERL------APEKDPAAIARARAELARLLAVLEARLAGGPYLAGDRFS 154

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1430951045 161 IADILAFCTIDFGKVVGLRItPEQPHLQDWHDRVSARSSAQA 202
Cdd:COG0625   155 IADIALAPVLRRLDRLGLDL-ADYPNLAAWLARLAARPAFQR 195

GST_N family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. cerevisiae GST protein, GTT2. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GTT2, a homodimer, exhibits GST activity with standard substrates. Strains with deleted GTT2 genes are viable but exhibit increased sensitivity to heat shock.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1430951045   1 MKVYELRRAPNARRVRMFLAEKGIEMEYQQVDLGAGENLAPAFLTKNPAGRIPVLELDDGTCLSETLAICRYFE 74
Cdd:cd03051     1 MKLYDSPTAPNPRRVRIFLAEKGIDVPLVTVDLAAGEQRSPEFLAKNPAGTVPVLELDDGTVITESVAICRYLE 74

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 1430951045   1 MKVYELRRAPNARRVRMFLAEKGIEMEYQQVDLGAGEnlAPAFLTKNPAGRIPVLElDDGTCLSETLAICRYFE 74
Cdd:cd00570     1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGE--QEEFLALNPLGKVPVLE-DGGLVLTESLAILEYLA 71

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045   1 MKVYELRRApNARRVRMFLAEKGIEMEYQQVDLGAGENLAPAFLTKNPAGRIPVLELDDGTcLSETLAICRYFEELHPE- 79
Cdd:PLN02395    3 LKVYGPAFA-SPKRALVTLIEKGVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIVDGDYK-IFESRAIMRYYAEKYRSq 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045  80 -PNLFGSTALERATIEMWSRfIEFNLWLPTGMA------FRHITGFYKDrERVFpewgEECKQQAQIWFDKLDARLAEVP 152
Cdd:PLN02395   81 gPDLLGKTIEERGQVEQWLD-VEATSYHPPLLNltlhilFASKMGFPAD-EKVI----KESEEKLAKVLDVYEARLSKSK 154

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1430951045 153 YIAGERFTIADI--LAFCTIDFGKVVGLRITPEQPHLQDWHDRVSARSS 199
Cdd:PLN02395  155 YLAGDFVSLADLahLPFTEYLVGPIGKAYLIKDRKHVSAWWDDISSRPA 203

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 1430951045   1 MKVYELRRAPNARRVRMFLAEKGIEMEYQQVDLGAGENLAPAFLTKNPAGRIPVLElDDGTCLSETLAICRYFEE 75
Cdd:pfam02798   3 LTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALE-DGGKKLTESRAILEYIAR 76

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1430951045   1 MKVYELRRAPNARRVRMFLAEKGIEMEYQQVDLGAGENLAPAFLTKNPAGRIPVLElDDGTCLSETLAICRYFE 74
Cdd:cd03042     1 MILYSYFRSSASYRVRIALNLKGLDYEYVPVNLLKGEQLSPAYRALNPQGLVPTLV-IDGLVLTQSLAIIEYLD 73

GST_N family, Class Beta subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit limited GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they also bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1430951045  15 VRMFLAEKGIEMEYQQVDLGAGENLAPAFLTKNPAGRIPVLELDDGTCLSETLAICRYFEELHP 78
Cdd:cd03057    14 PHIALEELGLPFELVRVDLRTKTQKGADYLAINPKGQVPALVLDDGEVLTESAAILQYLADLHP 77

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045   1 MKVYELRRAPNARRVRMFLAEKGIEMEYQQVDLGAGENLAPAFLTKNPAGRIPVLElDDGTCLSETLAICRYFEELHPE- 79
Cdd:PLN02473    3 VKVYGQIKAANPQRVLLCFLEKGIEFEVIHVDLDKLEQKKPEHLLRQPFGQVPAIE-DGDLKLFESRAIARYYATKYADq 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045  80 -PNLFGSTALERATIEMWSR-----FIEFNLWLPTGMAFRHITGFYKDRERVfpewgEECKQQAQIWFDKLDARLAEVPY 153
Cdd:PLN02473   82 gTDLLGKTLEHRAIVDQWVEvennyFYAVALPLVINLVFKPRLGEPCDVALV-----EELKVKFDKVLDVYENRLATNRY 156

                         170
                  ....*....|.
gi 1430951045 154 IAGERFTIADI 164
Cdd:PLN02473  157 LGGDEFTLADL 167

glutathione transferase;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1430951045  19 LAEKGIEMEYQQVDLGAGENLAPAFLTKNPAGRIPVLELDDGTcLSETLAICRYFEELHPEP 80
Cdd:PRK15113   26 LQEKGLPFELKTVDLDAGEHLQPTYQGYSLTRRVPTLQHDDFE-LSESSAIAEYLEERFAPP 86

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1430951045   2 KVYELRRAPNARRVRMFLAEKGIEMEYQQVDLgagENLAPAFLTKNPAGRIPVLELDDGTCLSETLAICRY 72
Cdd:cd03055    20 RLYSMRFCPYAQRARLVLAAKNIPHEVININL---KDKPDWFLEKNPQGKVPALEIDEGKVVYESLIICEY 87

GSH-dependent disulfide bond oxidoreductase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045  10 PNARRVRMFLAEKGIEMEYQQVDLGAGENLAPAFLTKNPAGRIPVL----ELDDGTCLS--ETLAICRYFEElhpEPNLF 83
Cdd:PRK13972   10 PNGHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIvdhsPADGGEPLSlfESGAILLYLAE---KTGLF 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045  84 GS-TALERATIEMWSrfiefnLWLPTGMA--FRHITGFYKDRERVFPEWGEECKQQAQIWFDKLDARLAEVPYIAGERFT 160
Cdd:PRK13972   87 LShETRERAATLQWL------FWQVGGLGpmLGQNHHFNHAAPQTIPYAIERYQVETQRLYHVLNKRLENSPWLGGENYS 160

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1430951045 161 IADILAFCTIDFGKVVGLRITpEQPHLQDWHDRVSARSS 199
Cdd:PRK13972  161 IADIACWPWVNAWTRQRIDLA-MYPAVKNWHERIRSRPA 198

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1430951045   4 YELRRAPNARRVRMFLAEKGIEMEYQQVDLgagENLAPAFLTKNPAGRIPVLELDDGTCLSETLAICRY 72
Cdd:cd03060     4 YSFRRCPYAMRARMALLLAGITVELREVEL---KNKPAEMLAASPKGTVPVLVLGNGTVIEESLDIMRW 69

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 1430951045  88 LERAtiemwsRFIEFNLWLPTGM--AFRHItgFYKDR---ERVFPEWGEECKQQAQIWFDKLDARLAEVPYIAGERFTIA 162
Cdd:cd03188     1 LERA------RLLEWLNFIASELhkAFGPL--FYPARwadDALAEEVKAAARERLERRLAYLDAQLAGGPYLLGDQFSVA 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1430951045 163 DILAFCTIDFGKVVGLRITPeQPHLQDWHDRVSARSSAQA 202
Cdd:cd03188    73 DAYLFVVLRWARAVGLDLSD-WPHLAAYLARVAARPAVQA 111

C-terminal, alpha helical domain of the Glutathione S-transferase family; Glutathione S-transferase (GST) family, C-terminal alpha helical domain; a large, diverse group of cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. In addition, GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. This family, also referred to as soluble GSTs, is the largest family of GSH transferases and is only distantly related to the mitochondrial GSTs (GSTK). Soluble GSTs bear no structural similarity to microsomal GSTs (MAPEG family) and display additional activities unique to their group, such as catalyzing thiolysis, reduction and isomerization of certain compounds. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. Based on sequence similarity, different classes of GSTs have been identified, which display varying tissue distribution, substrate specificities and additional specific activities. In humans, GSTs display polymorphisms which may influence individual susceptibility to diseases such as cancer, arthritis, allergy and sclerosis. Some GST family members with non-GST functions include glutaredoxin 2, the CLIC subfamily of anion channels, prion protein Ure2p, crystallins, metaxins, stringent starvation protein A, and aminoacyl-tRNA synthetases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045  98 RFIEFNLWLPTGMAFRHITGFYKDRERVFPEWGEECKQQAQIWFDKLDARLAEVPYIAGERFTIADILAFCTIDFGKVVG 177
Cdd:cd00299     2 RALEDWADATLAPPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEALG 81

                          90
                  ....*....|....*....
gi 1430951045 178 --LRITPEQPHLQDWHDRV 194
Cdd:cd00299    82 pyYDLLDEYPRLKAWYDRL 100

C-terminal, alpha helical domain of an unknown subfamily 2 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1430951045 131 EECKQQAQIwfdkLDARLAEVPYIAGERFTIADILAFCTIDfgKVVGLRIT-PEQPHLQDWHDRVSAR 197
Cdd:cd03180    46 AACNKLMAI----LDAQLARQAYLAGDRFTLADIALGCSVY--RWLELPIErPALPHLERWYARLSQR 107

C-terminal, alpha helical domain of Ure2p and related Glutathione S-transferase-like proteins; Glutathione S-transferase (GST) C-terminal domain family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p, YfcG and YghU from Escherichia coli, and related GST-like proteins. 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 thioredoxin-fold domain and a C-terminal alpha helical domain. The N-terminal thioredoxin-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. YfcG and YghU are two of the nine GST homologs in the genome of Escherichia coli. They display very low or no GSH transferase, but show very good disulfide bond oxidoreductase activity. YghU also shows modest organic hydroperoxide reductase activity. 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. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1430951045 144 LDARLAEVPYIAGERFTIADILAFCTIDFGKVVGLRITPEQPHLQDWHDRVSARSSAQ 201
Cdd:cd03178    52 LDKRLSDRPYLAGEEYSIADIALYPWTHYADLGGFADLSEYPNVKRWLERIAARPAVQ 109

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045  89 ERATIEMWSRFIEFNLWLPTGMAFRHITGF-YKDRERVFPEWGEECKQQAQIWFDKLDAR-LAEVPYIAGERFTIADILA 166
Cdd:cd03183     1 KRARVDEYLAWQHTNLRLGCAAYFWQKVLLpLFGGTPVSPEKVKKAEENLEESLDLLENKfLKDKPFLAGDEISIADLSA 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1430951045 167 FCTIDFGKVVGLRITPEQPHLQDWHDRVSARSS 199
Cdd:cd03183    81 ICEIMQPEAAGYDVFEGRPKLAAWRKRVKEAGN 113

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1430951045 129 WGEECKQQAQIWFDKLDARLAEVPYIAGERFTIADILAFCTIDFGKVVGLRITPEQ--PHLQDWHDR 193
Cdd:pfam13410   1 ALERAREQLRAALDALEARLADGPGLLGDRPTLADIALAPVLARLDAAYPGLDLREgyPRLRAWLER 67

C-terminal, alpha helical domain of Escherichia coli Yghu Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YghU-like subfamily; composed of the Escherichia coli YghU and related proteins. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. YghU is one of nine GST homologs in the genome of Escherichia coli. It is similar to Escherichia coli YfcG in that it has poor GSH transferase activity towards typical substrates. It shows modest reductase activity towards some organic hydroperoxides. Like YfcG, YghU also shows good disulfide bond oxidoreductase activity comparable to the activities of glutaredoxins and thioredoxins. YghU does not contain a redox active cysteine residue, and may use a bound thiol disulfide couple such as 2GSH/GSSG for activity. The crystal structure of YghU reveals two GSH molecules bound in its active site.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1430951045 132 ECKQQaqiwFDKLDARLAEVPYIAGERFTIADILAFCTidFGKVVGLRI--------TPEQPHLQDWHDRVSARSSAQ 201
Cdd:cd10292    44 EAKRQ----LDVLDRQLATHKYLAGDEYTIADMAIWPW--YGGLALGSLydaaefldVDEYKHVQRWAKDIAARPAVK 115

putative S-transferase; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1430951045 132 ECKQQaqiwFDKLDARLAEVPYIAGERFTIADILAFCTidFGKVVGLRI--------TPEQPHLQDWHDRVSARSSAQ 201
Cdd:PRK11752  182 EAKRQ----LDVLDKQLAEHEYIAGDEYTIADIAIWPW--YGNLVLGNLydaaefldVGSYKHVQRWAKEIAERPAVK 253

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045  89 ERATIEMWSRFIEFNLwLPTGMAFrhitgfykdrerVFPEWG---------EECKQQAQIWFDKLDARLAEVPYIAGERF 159
Cdd:cd03181     1 EAAQVLQWISFANSEL-LPAAATW------------VLPLLGiapynkkavDKAKEDLKRALGVLEEHLLTRTYLVGERI 67

                          90
                  ....*....|....
gi 1430951045 160 TIADILAFCTIDFG 173
Cdd:cd03181    68 TLADIFVASALLRG 81

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1430951045  14 RVRMFLAEKGIEMEYQQVDLGA-GENLApaflTKNPAGRIPVLeLDDGTCLSETLAICRYFEE 75
Cdd:cd03059    14 RVRIVLAEKGVSVEIIDVDPDNpPEDLA----ELNPYGTVPTL-VDRDLVLYESRIIMEYLDE 71

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1430951045 119 YKDRERvFPE-WGEECKQQAQIWFDKLDARLAEVPYIAGERFTIADI 164
Cdd:cd03196    28 YKYADR-YPEdDEEEYRAQAEEFLAELEARLSQHAYLFGDRPSLADY 73

C-terminal, alpha helical domain of GTT1-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae GTT1-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. cerevisiae GST protein, GTT1, and the Schizosaccharomyces pombe GST-III. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. GTT1, a homodimer, exhibits GST activity with standard substrates and associates with the endoplasmic reticulum. Its expression is induced after diauxic shift and remains high throughout the stationary phase. S. pombe GST-III is implicated in the detoxification of various metals.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045 141 FDKLDARLAEVPYIAGERFTIADILafctIDFGKVVGLRITP---EQPHLQDWHDRVSAR 197
Cdd:cd03189    67 LDFLEDHLAKHPYFAGDELTAADIM----MSFPLEAALARGPlleQYPNIAAYLERIEAR 122

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1430951045   3 VYELRRAPNARRVRMFLAEKGIEMEYQQVDLGAGENLAPAFLTKNPAGRIPVLeLDDGTCLSETLAICRYFE 74
Cdd:cd03052     3 LYHWTQSFSSQKVRLVIAEKGLRCEEYDVSLPLSEHNEPWFMRLNPTGEVPVL-IHGDNIICDPTQIIDYLE 73

glutaredoxin 2; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045   1 MKVYELRRAPNARRVRMFLAEKGIEMEyqQVDLGAGENLAPAFLTknpaGR--IPVLELDDGTCLSETLAICRYFEELHP 78
Cdd:PRK10387    1 MKLYIYDHCPFCVKARMIFGLKNIPVE--LIVLANDDEATPIRMI----GQkqVPILQKDDGSYMPESLDIVHYIDELDG 74

                          90       100
                  ....*....|....*....|
gi 1430951045  79 EPNLFGSTaleRATIEMWSR 98
Cdd:PRK10387   75 KPLLTGKR---SPAIEEWLR 91

C-terminal, alpha helical domain of an unknown subfamily 6 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 6; composed of uncharacterized bacterial proteins with similarity to GSTs, including Pseudomonas fluorescens GST with a known three-dimensional structure. 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. Though the three-dimensional structure of Pseudomonas fluorescens GST has been determined, there is no information on its functional characterization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430951045 123 ERVFPEWGEecKQQAQIW--FDKLDARLAEVPyiaGERFTIADILAFCTIDFgkvVGLRiTPEQ------PHLQDWHDRV 194
Cdd:cd03205    28 EKQHQPWIE--RQWGKIEraLDALEAELGDLP---GGRLTLGDIAVACALGY---LDFR-FPELdwraghPALAAWFARF 98

                  ....*...
gi 1430951045 195 SARSSAQA 202
Cdd:cd03205    99 EARPSFQA 106

C-terminal, alpha helical domain of an unknown subfamily 7 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 7; composed of uncharacterized 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1430951045 131 EECKQQAQIWFDKLDARLAEVPYIAGERFTIADILAFCTIDFGKVVGLRITPeQPHLQDWHDRVSA 196
Cdd:cd03206    32 ERARAISHRLLRLLDQHLAGRDWLAGDRPTIADVACYPYIALAPEGGVSLEP-YPAIRAWLARVEA 96