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 24762316  65 REVEAQVYQWIEFSVLYVAPGSkDKYVSKQLLADFNKLFASKSYLVGHFITLADLAVYYAIYDLVKSLSPVDKEVYLNLS 144
Cdd:cd10305   1 AEERAQVDQWLEYRVTQVAPAS-DKADAKSLLKELNSYLQDRTYLVGHKLTLADVVLYYGLHPIMKDLSPQEKEQYLNVS 79

                        90       100
                ....*....|....*....|..
gi 24762316 145 RWFDHLQNRADVHQGEPLLNFT 166
Cdd:cd10305  80 RWFDHVQHLPGIRQHLPLINFT 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 24762316  65 REVEAQVYQWIEFSVLYVAPGSkDKYVSKQLLADFNKLFASKSYLVGHFITLADLAVYYAIYDLVKSLSPVDKEVYLNLS 144
Cdd:cd10305   1 AEERAQVDQWLEYRVTQVAPAS-DKADAKSLLKELNSYLQDRTYLVGHKLTLADVVLYYGLHPIMKDLSPQEKEQYLNVS 79

                        90       100
                ....*....|....*....|..
gi 24762316 145 RWFDHLQNRADVHQGEPLLNFT 166
Cdd:cd10305  80 RWFDHVQHLPGIRQHLPLINFT 101

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24762316  69 AQVYQWIEFSVLYVAPG---------------SKDKYVSK--QLLADFNKLFASKSYLVGHFITLADLAVYYAIYDLVKs 131
Cdd:COG0625  91 ARVRQWLAWADGDLHPAlrnllerlapekdpaAIARARAElaRLLAVLEARLAGGPYLAGDRFSIADIALAPVLRRLDR- 169

                        90       100
                ....*....|....*....|..
gi 24762316 132 lSPVDKEVYLNLSRWFDHLQNR 153
Cdd:COG0625 170 -LGLDLADYPNLAAWLARLAAR 190

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 24762316  65 REVEAQVYQWIEFSVLYVAPGSkDKYVSKQLLADFNKLFASKSYLVGHFITLADLAVYYAIYDLVKSLSPVDKEVYLNLS 144
Cdd:cd10305   1 AEERAQVDQWLEYRVTQVAPAS-DKADAKSLLKELNSYLQDRTYLVGHKLTLADVVLYYGLHPIMKDLSPQEKEQYLNVS 79

                        90       100
                ....*....|....*....|..
gi 24762316 145 RWFDHLQNRADVHQGEPLLNFT 166
Cdd:cd10305  80 RWFDHVQHLPGIRQHLPLINFT 101

Glutathione S-transferase C-terminal-like, alpha helical domain of bifunctional Glutamyl-Prolyl-tRNA synthetase; Glutathione S-transferase (GST) C-terminal domain family, bifunctional GluRS-Prolyl-tRNA synthetase (GluProRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of GluProRS from higher 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 GluProRS may be involved in protein-protein interactions, mediating the formation of the multi-aaRS complex in higher eukaryotes. The multi-aaRS complex acts as a molecular hub 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 24762316  70 QVYQWIEFSVLYVapGSKDKYVSkqLLADFNKLFASKSYLVGHFITLADLAVYYAIYDlvKSLSPVDKEVYLNLSRWFDH 149
Cdd:cd10309   4 EVDHWISFSAGRL--SCDQDFSS--ALSYLDKALSLRTYLVGNSLTLADFAVWAALRG--NGEWLASKEKYVNVTRWFKF 77

                ...
gi 24762316 150 LQN 152
Cdd:cd10309  78 ISS 80

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 24762316  68 EAQVYQWIEFSVLYVAPGS------------KDKYVSKQLLADFNKLF-------ASKSYLVGHFITLADLAVYYA-IYD 127
Cdd:cd10294   2 CALVWQWVSFADNELTPAAcaaafpllglsgSDKQNQQRSLAELQRVLkvldcylKLRTYLVGEAITLADIAVACAlLLP 81

                        90       100
                ....*....|....*....|
gi 24762316 128 LVKSLSPVDKEVYLNLSRWF 147
Cdd:cd10294  82 FKYVLDPARRESLLNVTRWF 101

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 24762316  92 SKQLLADFNKLFASKSYLVGHFITLADLAVYYAIydlvksLSPVDKEVYLNLSRWFDHLQ 151
Cdd:cd10308  27 TDKGLEALNEYLADRSYISGYSPSQADVEVFDKL------KKAPDATKFPHLARWYRHIA 80

glutamate-tRNA ligase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24762316    4 VATVQKIANCLGVNPgkvQLNEEQVVTRTSGQKKSVAGFASILESLASESKSET--AQNSRASreveAQVYQWIEFSVLY 81
Cdd:PLN02907  17 IAAAKVAGVPLTIDP---SLKSGSAPTLLFSSGEKLTGTNVLLRYIARSASLPGfyGQDAFES----SQVDEWLDYAPTF 89

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24762316   82 VAPGSKDK---YVskqlladfNKLFASKSYLVGHFITLADLAVYYAIYDLVKSLSPVDKEV-YLNLSRWFD 148
Cdd:PLN02907  90 SSGSEFENaceYV--------DGYLASRTFLVGYSLTIADIAIWSGLAGSGQRWESLRKSKkYQNLVRWFN 152

C-terminal, alpha helical domain of GTT2-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the Saccharomyces 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 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. 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24762316  68 EAQVYQWiefsvlyvAPGSKDKYVskQLLADFNKLFASKSYLVGHFITLADLAVYYAIyDLVKSLS-PVDKEVYlNLSRW 146
Cdd:cd03182  39 EVQVPEW--------GERNKKRVI--DFLPVLDKRLAESPYVAGDRFSIADITAFVAL-DFAKNLKlPVPEELT-ALRRW 106

                        90
                ....*....|
gi 24762316 147 FDHLQNRADV 156
Cdd:cd03182 107 YERMAARPSA 116

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24762316    77 FSVLYVAPGSKDK----YVSKQL---LADFNKLFASKSYLVGHFITLADLAV-----YYAIYDLVKSLSPvdkevYLNLS 144
Cdd:pfam00043   9 ALLPYVPPEEKKEpevdEALEKVarvLSALEEVLKGQTYLVGDKLTLADIALapallWLYELDPACLREK-----FPNLK 83

                  ....*....
gi 24762316   145 RWFDHLQNR 153
Cdd:pfam00043  84 AWFERVAAR 92

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 24762316  93 KQLLADFNKLFASKSYLVGHFITLADLAVY--YA------IYDLVKSLspvDKEVYLNLSRWFDHLQNRADVHQG 159
Cdd:cd10292  46 KRQLDVLDRQLATHKYLAGDEYTIADMAIWpwYGglalgsLYDAAEFL---DVDEYKHVQRWAKDIAARPAVKRG 117