The crystal structures of glutathione S‐transferases isozymes 1–3 and 1–4 from <i>Anopheles dirus</i> species B

Oakley, A.J.; Harnnoi, Thasaneeya; Udomsinprasert, Rungrutai; Jirajaroenrat, Kanya; Ketterman, Albert J.; Wilce, Matthew C. J.

doi:10.1110/ps.ps.21201

Cited by 74 publications

(51 citation statements)

References 59 publications

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“…The linker of 7 residues (Lys 57 -Ser 63 ), in which the peptide from Glu 58 to Leu 61 forms a 3 10 helix, connects the two domains. A short-turn helix is also found in the linker connecting two domains in the structures of GSTs from maize (22) and mosquito (23). The C-terminal domain (AIMP3-C) consists of a bundle of five helices (␣3 to ␣7) (Thr 64 -Tyr 152 ) and a following coiled region (Pro 153 -Leu 169 ).…”

Section: Resultsmentioning

confidence: 99%

Determination of Three-dimensional Structure and Residues of the Novel Tumor Suppressor AIMP3/p18 Required for the Interaction with ATM

Kim

Park

Choi

et al. 2008

Journal of Biological Chemistry

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Although AIMP3/p18 is normally associated with the multitRNA synthetase complex via its specific interaction with methionyl-tRNA synthetase, it also works as a tumor suppressor by interacting with ATM, the upstream kinase of p53. To understand the molecular interactions of AIMP3 and the mechanisms involved, we determined the crystal structure of AIMP3 at 2.0-Å resolution and identified its potential sites of interaction with ATM. AIMP3 contains two distinct domains linked by a 7-amino acid (Lys 57 -Ser 63 ) peptide, which contains a 3 10 helix. The 56-amino acid N-terminal domain consists of two helices into which three antiparallel ␤ strands are inserted, and the 111-amino acid C-terminal domain contains a bundle of five helices (Thr 64 -Tyr 152 ) followed by a coiled region (Pro 153 -Leu 169 ). Structural analyses revealed homologous proteins such as yeast glutamyl-tRNA synthetase, Arc1p, EF1B␥, and glutathione S-transferase and suggested two potential molecular binding sites. Moreover, mutations at the C-terminal putative binding site abolished the interaction between AIMP3 and ATM and the ability of AIMP3 to activate p53. Thus, this work identified the two potential molecular interaction sites of AIMP3 and determined the residues critical for its tumor-suppressive activity through the interaction with ATM.Although aminoacyl-tRNA synthetases (ARSs) 4 catalyze the ligation of specific amino acids to their cognate tRNAs, they are multifunctional proteins that are involved in the regulation of diverse signal pathways (1). Several ARSs of higher eukaryotes form an intriguing macromolecular protein complex with three non-enzymatic factors, designated AIMPs (ARS-interacting multifunctional proteins), which are also multiply involved in various biological processes. Of these factors, AIMP1/p43 is secreted as a cytokine that functions in immune response (2, 3), angiogenesis (4), and wound-healing processes (5) and also as a hormone that regulates glucose metabolism (6). AIMP2/p38 has been shown to mediate transforming growth factor-␤ signaling for c-Myc down-regulation (7). AIMP3/p18 binds to the multi-ARS complex by specifically interacting with methionyltRNA synthetase (MRS) and is translocated to the nucleus to activate p53 through the interaction with kinases such as ATM (ataxia telangiectasia mutated) and ATR (ATM-and Rad3-related) in response to DNA damage (8) or oncogenic stress (9). To understand the multifunctionality and regulation of the components of the multi-ARS complex, it is important to determine the three-dimensional structures of the components as well as the whole complex. So far, only the three-dimensional structures of the partial domains of the complex-forming ARSs such as glutamylprolyl-tRNA synthetase (10, 11), aspartyltRNA synthetase (12), and AIMP1/p43 (13, 14) have been elucidated. Here, we report the crystal structure of full-length AIMP3 and the residues and location required for the interaction with ATM. EXPERIMENTAL PROCEDURESCloning, Expression, and Purification of Human AIMP3-The cDN...

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Section: Resultsmentioning

confidence: 99%

Determination of Three-dimensional Structure and Residues of the Novel Tumor Suppressor AIMP3/p18 Required for the Interaction with ATM

Kim

Park

Choi

et al. 2008

Journal of Biological Chemistry

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“…It adds to the ␣-helix domain, near the C-terminal end of helix ␣6, so that it also interacts with the thioredoxin-like domain via the short loop that connects the strand ␤1 and the ␣-helix ␣1 and via the long loop that goes from ␤2 to ␣2. Helix ␣9 is a structural characteristic of GST Omega (10) and is also present in GST Tau (45) and GST Delta (46). In these GSTs, the few residues that follow ␣9 (when they exist) go toward the thioredoxin-like domain to interact with the loops ␤1-␣1 and ␤2-␣2.…”

Section: Gshmentioning

confidence: 99%

Glutathione Transferases of Phanerochaete chrysosporium

Meux

Prosper²,

Ngadin

et al. 2011

Journal of Biological Chemistry

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The white rot fungus Phanerochaete chrysosporium, a saprophytic basidiomycete, possesses a large number of cytosolic glutathione transferases, eight of them showing similarity to the Omega class. PcGSTO1 (subclass I, the bacterial homologs of which were recently proposed, based on their enzymatic function, to constitute a new class of glutathione transferase named S-glutathionyl-(chloro)hydroquinone reductases) and PcGSTO3 (subclass II related to mammalian homologs) have been investigated in this study. Biochemical investigations demonstrate that both enzymes are able to catalyze deglutathionylation reactions thanks to the presence of a catalytic cysteinyl residue. This reaction leads to the formation of a disulfide bridge between the conserved cysteine and the removed glutathione from their substrate. The substrate specificity of each isoform differs. In particular PcGSTO1, in contrast to PcGSTO3, was found to catalyze deglutathionylation of S-glutathionyl-p-hydroquinone substrates. The three-dimensional structure of PcGSTO1 presented here confirms the hypothesis that it belongs not only to a new biological class but also to a new structural class that we propose to name GST xi. Indeed, it shows specific features, the most striking ones being a new dimerization mode and a catalytic site that is buried due to the presence of long loops and that contains the catalytic cysteine.

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“…The currently recognized classes of cytosolic GSTs (with references to representative structures) are alpha (Sinning et al 1993), beta (Rossjohn et al 1998b), delta (Wilce et al 1995;Oakley et al 2001), epsilon (Sawicki et al 2003), zeta (Polekhina et al 2001), theta (Rossjohn et al 1998a), mu , nu (Schuller et al 2005), pi (Reinemer et al 1992), sigma (Ji et al 1995;Kanaoka et al 1997), tau (Thom et al 2002), phi (Reinemer et al 1996) and omega (Board et al 2000). The mitochondrial GSTs share a deep evolutionary relationship with the cytosolic GSTs (discussed below) and are designated class kappa.…”

Section: Introductionmentioning

confidence: 99%

Glutathione transferases: a structural perspective

Oakley

2011

Drug Metabolism Reviews

329

240

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The glutathione transferases (GSTs) are one of the most important families of detoxifying enzymes in nature. The classic activity of the GSTs is conjugation of compounds with electrophilic centers to the tripeptide glutathione (GSH), but many other activities are now associated with GSTs, including steroid and leukotriene biosynthesis, peroxide degradation, double-bond cis-trans isomerization, dehydroascorbate reduction, Michael addition, and noncatalytic "ligandin" activity (ligand binding and transport). Since the first GST structure was determined in 1991, there has been an explosion in structural data across GSTs of all three families: the cytosolic GSTs, the mitochondrial GSTs, and the membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG family). In this review, the major insights into GST structure and function will be discussed. AbstractThe glutathione transferases (GSTs) are one of the most important families of detoxifying enzymes in nature. The classic activity of the GSTs is conjugation of compounds with electrophilic centers to the tripeptide glutathione (GSH), but many other activities are now associated with GSTs, including steroid and leukotriene biosynthesis, peroxide degradation, double-bond cis-trans isomerization, dehydroascorbate reduction, Michael addition, and non-catalytic "ligandin" activity (ligand binding and transport). Since the first GST structure was determined in 1991, there has been an explosion in structural data across GSTs of all three families: the cytosolic GSTs, the mitochondrial GSTs and the membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG family). In this review, the major insights into GST structure and function will be discussed.

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The crystal structures of glutathione S‐transferases isozymes 1–3 and 1–4 from Anopheles dirus species B

Cited by 74 publications

References 59 publications

Determination of Three-dimensional Structure and Residues of the Novel Tumor Suppressor AIMP3/p18 Required for the Interaction with ATM

Determination of Three-dimensional Structure and Residues of the Novel Tumor Suppressor AIMP3/p18 Required for the Interaction with ATM

Glutathione Transferases of Phanerochaete chrysosporium

Glutathione transferases: a structural perspective

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