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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1897357886  28 KVPVLQNNnGPALTGLVTIACHLvkEAKRPE--LLGDDAEQRAVVQQWLE--------------HRITKLDN-----CSK 86
Cdd:COG0625    52 KVPVLVDD-GLVLTESLAILEYL--AERYPEppLLPADPAARARVRQWLAwadgdlhpalrnllERLAPEKDpaaiaRAR 128

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1897357886  87 EEVKVILKDLNRYLEDKVYLAGNVFTLADILMYYGIHHI-IVELAIQEkecYLNVSRWFDHIQHYPGIRHHLPP 159
Cdd:COG0625   129 AELARLLAVLEARLAGGPYLAGDRFSIADIALAPVLRRLdRLGLDLAD---YPNLAAWLARLAARPAFQRALAA 199

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 1897357886  86 KEEVKVILKDLNRYLEDKVYLAGNVFTLADILMY--YGIHHIIVELAIQEKecYLNVSRWFDHI 147
Cdd:pfam00043  28 LEKVARVLSALEEVLKGQTYLVGDKLTLADIALApaLLWLYELDPACLREK--FPNLKAWFERV 89

Glutathione S-transferase C-terminal-like, alpha helical domain of various Aminoacyl-tRNA synthetases and similar domains; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl-tRNA synthetase (AaRS)-like subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of some eukaryotic AaRSs, as well as similar domains found in proteins involved in protein synthesis including Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 2 (AIMP2), AIMP3, and eukaryotic translation Elongation Factor 1 beta (eEF1b). AaRSs comprise a family of enzymes that catalyze the coupling of amino acids with their matching tRNAs. This involves the formation of an aminoacyl adenylate using ATP, followed by the transfer of the activated amino acid to the 3'-adenosine moiety of the tRNA. AaRSs may also be involved in translational and transcriptional regulation, as well as in tRNA processing. AaRSs in this subfamily include GluRS from lower eukaryotes, as well as GluProRS, MetRS, and CysRS from higher eukaryotes. AIMPs are non-enzymatic cofactors that play critical roles in the assembly and formation of a macromolecular multi-tRNA synthetase protein complex found in higher eukaryotes. The GST_C-like domain is involved in protein-protein interactions, mediating the formation of aaRS complexes such as the MetRS-Arc1p-GluRS ternary complex in lower eukaryotes and the multi-aaRS complex in higher eukaryotes, that act as molecular hubs for protein synthesis. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1897357886  68 AVVQQWLEhRITKLDncSKEEVKVILKDLNRYLEDKVYLAGNVFTLADILMYYGIHHIIVELAIQEKECYLNVSRWFDHI 147
Cdd:cd10289     3 AQVDQWLD-LAGSLL--KGKELEALLKSLNSYLASRTFLVGYSLTLADVAVFSALYPSGQKLSDKEKKKFPHVTRWFNHI 79

                  ...
gi 1897357886 148 QHY 150
Cdd:cd10289    80 QNL 82

glutamate-tRNA ligase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1897357886  29 VPVLQNNNGPALTGLVTIACHLVKEAKRPELLGDDAEQRAVVQQWLEHRITKLdncSKEEVKVILKDLNRYLEDKVYLAG 108
Cdd:PLN02907   38 APTLLFSSGEKLTGTNVLLRYIARSASLPGFYGQDAFESSQVDEWLDYAPTFS---SGSEFENACEYVDGYLASRTFLVG 114

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1897357886 109 NVFTLADILMYYGIHHIIVEL-AIQEKECYLNVSRWFDHI 147
Cdd:PLN02907  115 YSLTIADIAIWSGLAGSGQRWeSLRKSKKYQNLVRWFNSI 154

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1897357886  87 EEVKVILKDLNRYLEDKVYLAGNVFTLADILMyYGIHHIIVELAIQEKECYLNVSRWFDHIQHYPGI 153
Cdd:cd03178    43 DEVKRLYGVLDKRLSDRPYLAGEEYSIADIAL-YPWTHYADLGGFADLSEYPNVKRWLERIAARPAV 108

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 1897357886  90 KVILKDLNRYLEDKVYLAGNVFTLADILMYYGIHhiivELAIQEKecYLNVSRWFDHIQHY 150
Cdd:cd10308    28 DKGLEALNEYLADRSYISGYSPSQADVEVFDKLK----KAPDATK--FPHLARWYRHIASF 82

C-terminal, alpha helical domain of Class Delta and Epsilon Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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 1897357886  75 EHRITKLDNCskeevkviLKDLNRYLEDKVYLAGNVFTLADIlmyyGIHHIIVELAIQ--EKECYLNVSRWFDHIQ 148
Cdd:cd03177    37 EEKLDKLEEA--------LEFLETFLEGSDYVAGDQLTIADL----SLVATVSTLEVVgfDLSKYPNVAAWYERLK 100

Glutathione S-transferase C-terminal-like, alpha helical domain of Glutamyl-tRNA synthetase; Glutathione S-transferase (GST) C-terminal domain family, Glutamyl-tRNA synthetase (GluRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of GluRS from lower eukaryotes. Aminoacyl-tRNA synthetases (aaRSs) comprise a family of enzymes that catalyze the coupling of amino acids with their matching tRNAs. This involves the formation of an aminoacyl adenylate using ATP, followed by the transfer of the activated amino acid to the 3'-adenosine moiety of the tRNA. AaRSs may also be involved in translational and transcriptional regulation, as well as in tRNA processing. The GST_C-like domain of GluRS is involved in protein-protein interactions. This domain mediates the formation of the MetRS-Arc1p-GluRS ternary complex found in lower eukaryotes, which is considered an evolutionary intermediate between prokaryotic aaRS and the multi-aaRS complex found in higher eukaryotes. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1897357886  64 AEQRAVVQQWLEHRITKLDNCSKEEVKVILKDLNRYLEDKVYLAGNVFTLADILMYYGIHHIIVELAIQEKECYLNVSRW 143
Cdd:cd10306     1 NGDKEQVAEWIDFATTLLVLKDFKALSQALEELDSHLTLRTFIVGYSLSLADIAVWGALRGNGVAGSLIKNKVYVNLSRW 80

                  ....
gi 1897357886 144 FDHI 147
Cdd:cd10306    81 FSFL 84

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 1897357886  86 KEEVKVILKDLNRYLEDKVYLAGNVFTLADILMY--YGIHHIIVELAIQEKecYLNVSRWFDHI 147
Cdd:pfam00043  28 LEKVARVLSALEEVLKGQTYLVGDKLTLADIALApaLLWLYELDPACLREK--FPNLKAWFERV 89

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 1897357886  88 EVKVILKDLNRYLEDKVYLAGNVFTLADILMY--YG------IHHIIVELAIQEkecYLNVSRWFDHIQHYPGIR 154
Cdd:cd10292    44 EAKRQLDVLDRQLATHKYLAGDEYTIADMAIWpwYGglalgsLYDAAEFLDVDE---YKHVQRWAKDIAARPAVK 115

Glutathione S-transferase C-terminal-like, alpha helical domain of Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 2; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein (AIMP) 2 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. AIMP2, also called p38 or JTV-1, contains a C-terminal domain with similarity to the C-terminal alpha helical domain of GSTs. It plays an important role in the control of cell fate via antiproliferative (by enhancing the TGF-beta signal) and proapoptotic (activation of p53 and TNF-alpha) activities. Its roles in the control of cell proliferation and death suggest that it is a potent tumor suppressor. AIMP2 heterozygous mice with lower than normal expression of AIMP2 show high susceptibility to tumorigenesis. AIMP2 is also a substrate of Parkin, an E3 ubiquitin ligase that is involved in the ubiquitylation and proteasomal degradation of its substrates. Mutations in the Parkin gene is found in 50% of patients with autosomal-recessive early-onset parkinsonism. The accumulation of AIMP2, due to impaired Parkin function, may play a role in the pathogenesis of Parkinson's disease.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1897357886  59 LLGD---DAEQRAVVQQWLEHRITKLDNCSKEEVKVILKDLNRYLEDKVYLAGNVFTLADILMYYGIHHIIVELAIQEke 135
Cdd:cd03200     7 LLGDesdDPVNATLIDSWVDTAIFQLLEGSSKEKAAVLRALNSALGRSPWLVGSEPTVADIALWSAVLQTGLASGAPA-- 84

                  ....*...
gi 1897357886 136 cylNVSRW 143
Cdd:cd03200    85 ---NVQRW 89

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
                  ....*....|....*....|....*....|....
gi 1897357886  86 KEEVKVILKDLNRYLEDKVYLAGNVFTLADILMY 119
Cdd:cd00299    38 REELPALLAALEQLLAGRPYLAGDQFSLADVALA 71

Glutathione S-transferase C-terminal-like, alpha helical domain of vertebrate Valyl-tRNA synthetase; Glutathione S-transferase (GST) C-terminal domain family, Valyl-tRNA synthetase (ValRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of human ValRS and its homologs from other vertebrates such as frog and zebrafish. Aminoacyl-tRNA synthetases (aaRSs) comprise a family of enzymes that catalyze the coupling of amino acids with their matching tRNAs. This involves the formation of an aminoacyl adenylate using ATP, followed by the transfer of the activated amino acid to the 3'-adenosine moiety of the tRNA. AaRSs may also be involved in translational and transcriptional regulation, as well as in tRNA processing. They typically form large stable complexes with other proteins. 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. The GST_C-like domain of ValRS from higher eukaryotes is likely involved in protein-protein interactions, to mediate the formation of the multi-aaRS complex that acts as a molecular hub to coordinate protein synthesis. ValRSs from prokaryotes and lower eukaryotes, such as fungi and plants, do not appear to contain this GST_C-like domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1897357886  66 QRAVVQQWL---EHRIT------------------KLDNCSKEEVKVILKDLNRYLEDKVYLAGNVFTLADILMYYGI-- 122
Cdd:cd10294     1 ACALVWQWVsfaDNELTpaacaaafpllglsgsdkQNQQRSLAELQRVLKVLDCYLKLRTYLVGEAITLADIAVACALll 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1897357886 123 -HHIIVELAIQEKecYLNVSRWFDHIQHYPGIRHHLPPVVVL 163
Cdd:cd10294    81 pFKYVLDPARRES--LLNVTRWFLTCVNQPEFLAVLGEVSLC 120