Glutathione S-transferase C-terminal-like, alpha helical domain of Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 3; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein (AIMP) 3 subfamily; AIMPs are non-enzymatic cofactors that play critical roles in the assembly and formation of a macromolecular multi-tRNA synthetase protein complex that functions as a molecular hub to coordinate protein synthesis. There are three AIMPs, named AIMP1-3, which play diverse regulatory roles. AIMP3, also called p18 or eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1), contains a C-terminal domain with similarity to the C-terminal alpha helical domain of GSTs. It specifically interacts with methionyl-tRNA synthetase (MetRS) and is translocated to the nucleus during DNA synthesis or in response to DNA damage and oncogenic stress. In the nucleus, it interacts with ATM and ATR, which are upstream kinase regulators of p53. It appears to work against DNA damage in cooperation with AIMP2, and similar to AIMP2, AIMP3 is also a haploinsufficient tumor suppressor. AIMP3 transgenic mice have shorter lifespans than wild-type mice and they show characteristics of progeria, suggesting that AIMP3 may also be involved in cellular and organismal aging.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024472734  72 AEEKAVVHQWLEYRVTQVGRQSSREDTRTVLKDLNAHLEDKVYLAGNSFTLADILMYYGLHHVMVDLTVQEKEIYLNVSR 151
Cdd:cd10305     1 AEERAQVDQWLEYRVTQVAPASDKADAKSLLKELNSYLQDRTYLVGHKLTLADVVLYYGLHPIMKDLSPQEKEQYLNVSR 80

                          90       100
                  ....*....|....*....|.
gi 2024472734 152 WFNHIQHYPGVRQHLTNVIFI 172
Cdd:cd10305    81 WFDHVQHLPGIRQHLPLINFT 101

Glutathione S-transferase C-terminal-like, alpha helical domain of Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 3; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein (AIMP) 3 subfamily; AIMPs are non-enzymatic cofactors that play critical roles in the assembly and formation of a macromolecular multi-tRNA synthetase protein complex that functions as a molecular hub to coordinate protein synthesis. There are three AIMPs, named AIMP1-3, which play diverse regulatory roles. AIMP3, also called p18 or eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1), contains a C-terminal domain with similarity to the C-terminal alpha helical domain of GSTs. It specifically interacts with methionyl-tRNA synthetase (MetRS) and is translocated to the nucleus during DNA synthesis or in response to DNA damage and oncogenic stress. In the nucleus, it interacts with ATM and ATR, which are upstream kinase regulators of p53. It appears to work against DNA damage in cooperation with AIMP2, and similar to AIMP2, AIMP3 is also a haploinsufficient tumor suppressor. AIMP3 transgenic mice have shorter lifespans than wild-type mice and they show characteristics of progeria, suggesting that AIMP3 may also be involved in cellular and organismal aging.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024472734  72 AEEKAVVHQWLEYRVTQVGRQSSREDTRTVLKDLNAHLEDKVYLAGNSFTLADILMYYGLHHVMVDLTVQEKEIYLNVSR 151
Cdd:cd10305     1 AEERAQVDQWLEYRVTQVAPASDKADAKSLLKELNSYLQDRTYLVGHKLTLADVVLYYGLHPIMKDLSPQEKEQYLNVSR 80

                          90       100
                  ....*....|....*....|.
gi 2024472734 152 WFNHIQHYPGVRQHLTNVIFI 172
Cdd:cd10305    81 WFDHVQHLPGIRQHLPLINFT 101

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024472734  95 REDTRTVLKDLNAHLEDKVYLAGNSFTLADILMYYGL-HHVMVDLTVqEKEIYLNVSRWFNHI 156
Cdd:pfam00043  28 LEKVARVLSALEEVLKGQTYLVGDKLTLADIALAPALlWLYELDPAC-LREKFPNLKAWFERV 89

Glutathione S-transferase C-terminal-like, alpha helical domain of Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 3; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein (AIMP) 3 subfamily; AIMPs are non-enzymatic cofactors that play critical roles in the assembly and formation of a macromolecular multi-tRNA synthetase protein complex that functions as a molecular hub to coordinate protein synthesis. There are three AIMPs, named AIMP1-3, which play diverse regulatory roles. AIMP3, also called p18 or eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1), contains a C-terminal domain with similarity to the C-terminal alpha helical domain of GSTs. It specifically interacts with methionyl-tRNA synthetase (MetRS) and is translocated to the nucleus during DNA synthesis or in response to DNA damage and oncogenic stress. In the nucleus, it interacts with ATM and ATR, which are upstream kinase regulators of p53. It appears to work against DNA damage in cooperation with AIMP2, and similar to AIMP2, AIMP3 is also a haploinsufficient tumor suppressor. AIMP3 transgenic mice have shorter lifespans than wild-type mice and they show characteristics of progeria, suggesting that AIMP3 may also be involved in cellular and organismal aging.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024472734  72 AEEKAVVHQWLEYRVTQVGRQSSREDTRTVLKDLNAHLEDKVYLAGNSFTLADILMYYGLHHVMVDLTVQEKEIYLNVSR 151
Cdd:cd10305     1 AEERAQVDQWLEYRVTQVAPASDKADAKSLLKELNSYLQDRTYLVGHKLTLADVVLYYGLHPIMKDLSPQEKEQYLNVSR 80

                          90       100
                  ....*....|....*....|.
gi 2024472734 152 WFNHIQHYPGVRQHLTNVIFI 172
Cdd:cd10305    81 WFDHVQHLPGIRQHLPLINFT 101

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 2024472734  94 SREDTRTVLKDLNAHLEDKVYLAGNSFTLADI----LMYYGLHHVMvDLTVQEKeiYLNVSRWFNHIQHYPGVRQHLTNV 169
Cdd:cd03181    41 AKEDLKRALGVLEEHLLTRTYLVGERITLADIfvasALLRGFETVL-DPEFRKK--YPNVTRWFNTVVNQPKFKAVFGEV 117

                  ....
gi 2024472734 170 IFIK 173
Cdd:cd03181   118 KLCE 121

Glutathione S-transferase C-terminal-like, alpha helical domain of eukaryotic translation Elongation Factor 1 beta; Glutathione S-transferase (GST) C-terminal domain family, eukaryotic translation Elongation Factor 1 beta (eEF1b) subfamily; eEF1b is a component 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. eEF1b contains a GST_C-like alpha helical domain at the N-terminal region and a C-terminal guanine nucleotide exchange domain. The GST_C-like domain likely functions as a protein-protein interaction domain, similar to the function of the GST_C-like domains of EF1Bgamma and various aminoacyl-tRNA synthetases (aaRSs) from higher eukaryotes.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2024472734  97 DTRTVLKDLNAHLEDKVYLAGNSFTLADILMYYGLHHVMVDltvqekEIYLNVSRWFNHIQHY 159
Cdd:cd10308    26 KTDKGLEALNEYLADRSYISGYSPSQADVEVFDKLKKAPDA------TKFPHLARWYRHIASF 82

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2024472734  95 REDTRTVLKDLNAHLEDKVYLAGNSFTLADILMY----YGLHHVMVDLtvqekEIYLNVSRWFNHIQHYPGVRQ 164
Cdd:cd03178    42 TDEVKRLYGVLDKRLSDRPYLAGEEYSIADIALYpwthYADLGGFADL-----SEYPNVKRWLERIAARPAVQK 110

Glutathione S-transferase C-terminal-like, alpha helical domain of the Aminoacyl tRNA synthetase cofactor 1 and similar proteins; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl tRNA synthetase cofactor 1 (Arc1p)-like subfamily; Arc1p, also called GU4 nucleic binding protein 1 (G4p1) or p42, is a tRNA-aminoacylation and nuclear-export cofactor. It contains a domain in the N-terminal region with similarity to the C-terminal alpha helical domain of GSTs. This domain mediates the association of the aminoacyl tRNA synthetases (aaRSs), MetRS and GluRS, in yeast to form a stable stoichiometric ternany complex. The GST_C-like domain of Arc1p is a protein-protein interaction domain containing two binding sites which enable it to bind the two aaRSs simultaneously and independently. The MetRS-Arc1p-GluRS complex selectively recruits and aminoacylates its cognate tRNAs without additional cofactors. Arc1p also plays a role in the transport of tRNA from the nucleus to the cytoplasm. It may also control the subcellular distribution of GluRS in the cytoplasm, nucleoplasm, and the mitochondrial matrix.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024472734  73 EEKAVVHQWLEYrvtqVGRQSSREDTRTVLKDLNAHLEDKVYLAGNSF-TLADILMYYGLHHVMVDLTVQEK---EIYLN 148
Cdd:cd10304     2 EQSAEVAQWLSV----AKSGPVSKDVQETLGQLNLHLRTRTFLLGTGKpSVADVAVFEAVLPVVKEWSDEVKtgyAKYRH 77

                          90
                  ....*....|..
gi 2024472734 149 VSRWFNHIQHYP 160
Cdd:cd10304    78 ILRWVDYVQNLL 89

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024472734  95 REDTRTVLKDLNAHLEDKVYLAGNSFTLADILMYYGLHHV---MVDLtvqekEIYLNVSRWFNHIQHYPG 161
Cdd:cd03206    35 RAISHRLLRLLDQHLAGRDWLAGDRPTIADVACYPYIALApegGVSL-----EPYPAIRAWLARVEALPG 99

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 2024472734 100 TVLKDLNAHLEDKVYLAGNSFTLADILMYYGLhhVMVDLTVQEKEIYLNVSRWFNHIQHYP 160
Cdd:cd03189    65 RHLDFLEDHLAKHPYFAGDELTAADIMMSFPL--EAALARGPLLEQYPNIAAYLERIEARP 123

C-terminal, alpha helical domain of an unknown subfamily 8 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 8; composed of Agrobacterium tumefaciens GST and other 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. The three-dimensional structure of Agrobacterium tumefaciens GST has been determined but there is no information on its functional characterization.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2024472734  91 RQSSREDTRTVLKDLNAHLEDKVYLAGNSFTLADILMYYGL 131
Cdd:cd03207    34 IAAAYGDLDERLAALEAALAGRPYLVGERFSAADLLLASVL 74

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024472734  92 QSSREDTRTVLKDLNAHLEDKVYLAGNSFTLADILM------YYGLHhvmvdltvQEKEIYLNVSRWFNHIQHYPG 161
Cdd:cd03180    42 AASLAACNKLMAILDAQLARQAYLAGDRFTLADIALgcsvyrWLELP--------IERPALPHLERWYARLSQRPA 109

glutathionine S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024472734  36 QIPILQTNSGPGLTGLITIASHLVKQAKKEQLL---GSSAEEKAVvhQWLEYRVTQVGRQSS---REDT--------RTV 101
Cdd:PRK10542   51 QVPALLLDDGTLLTEGVAIMQYLADSVPDRQLLapvGSLSRYHTI--EWLNYIATELHKGFTplfRPDTpeeykptvRAQ 128

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024472734 102 LKD----LNAHLEDKVYLAGNSFTLADILMYYGL---HHVMVDLtvqekEIYLNVSRWFNHIQHYPGVRQHL 166
Cdd:PRK10542  129 LEKkfqyVDEALADEQWICGQRFTIADAYLFTVLrwaYAVKLNL-----EGLEHIAAYMQRVAERPAVAAAL 195

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 2024472734  75 KAVVHQWLEYRVTQVGRQSSREDTRTVLKDLNAHLEDKVYLAGNSFTLADILMYYGLHHV-MVDLTVQEKEIYLNVSRWF 153
Cdd:cd00299    18 RLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLeALGPYYDLLDEYPRLKAWY 97

                  .
gi 2024472734 154 N 154
Cdd:cd00299    98 D 98

putative S-transferase; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024472734 105 LNAHLEDKVYLAGNSFTLADILMY--YG------LHHVMVDLTVQEkeiYLNVSRWFNHIQHYPGVR 163
Cdd:PRK11752  190 LDKQLAEHEYIAGDEYTIADIAIWpwYGnlvlgnLYDAAEFLDVGS---YKHVQRWAKEIAERPAVK 253

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 2024472734  74 EKAVVHQWLEYRVTQV-------------GRQSSREDTRTVLKD--------LNAHLEDKVYLAGNSFTLADILMYYGL- 131
Cdd:cd03188     2 ERARLLEWLNFIASELhkafgplfyparwADDALAEEVKAAARErlerrlayLDAQLAGGPYLLGDQFSVADAYLFVVLr 81

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2024472734 132 --HHVMVDLTVqekeiYLNVSRWFNHIQHYPGVRQ 164
Cdd:cd03188    82 waRAVGLDLSD-----WPHLAAYLARVAARPAVQA 111