Structural Understanding of the Glutathione-dependent Reduction Mechanism of Glutathionyl-Hydroquinone Reductases

Green, Abigail R.; Hayes, Robert P.; Xun, Luying; Kang, ChulHee

doi:10.1074/jbc.m112.395541

Cited by 15 publications

(36 citation statements)

References 24 publications

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“…Superimposed structures of TvGSTX1 WT and TvGSTX3 WT indicate a high degree of likeness (rmsd of 0.569 A for 488 Ca). On one hand, the residues that line the putative quinone-binding site (H site) of TvGSTX1 are identical to those suggested from the structures of PcGSTX1 [8], ScECM4 [15], and EcYqjG [14]. 2).…”

Section: Tvgstx1 Reduces Gs-men While Tvgstx3 Reduces Both Gs-men Andmentioning

confidence: 66%

“…GSTXs have been initially named glutathionylhydroquinone reductases (GHRs) and such activity was not detected for GSTO isoforms [18,20]. Green and coworkers [14] proposed that three tyrosine residues and a cysteine within the active site contribute to the catalytic activity of Xi GSTs. First, the attack of the substrate by the catalytic thiolate together with an acid catalysis by the tyrosine cluster result in a mixed disulfide bond Cys-S-SG and a protonated hydroquinone.…”

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confidence: 99%

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Trametes versicolor glutathione transferase Xi 3, a dual Cys‐GST with catalytic specificities of both Xi and Omega classes

et al. 2018

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Glutathione transferases (GSTs) from the Xi and Omega classes have a catalytic cysteine residue, which gives them reductase activities. Until now, they have been assigned distinct substrates. While Xi GSTs specifically reduce glutathionyl-(hydro)quinones, Omega GSTs are specialized in the reduction of glutathionyl-acetophenones. Here, we present the biochemical and structural analysis of TvGSTX1 and TvGSTX3 isoforms from the wood-degrading fungus Trametes versicolor. TvGSTX1 reduces GS-menadione as expected, while TvGSTX3 reduces both Xi and Omega substrates. An in-depth structural analysis indicates a broader active site for TvGSTX3 due to specific differences in the nature of the residues situated in the C-terminal helix α9. This feature could explain the catalytic duality of TvGSTX3. Based on phylogenetic analysis, we propose that this duality might exist in saprophytic fungi and ascomycetes.

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Section: Tvgstx1 Reduces Gs-men While Tvgstx3 Reduces Both Gs-men Andmentioning

confidence: 66%

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confidence: 99%

Trametes versicolor glutathione transferase Xi 3, a dual Cys‐GST with catalytic specificities of both Xi and Omega classes

et al. 2018

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“…ITC measurements were carried out in a VP-ITC instrument (MicroCal) as described previously (Green et al, 2012), with the exception that enzyme concentration was 50 mM and the buffer used was 50 mM sodium phosphate, pH 6.5. CD spectra for both wild-type and mutant SbCOMT enzymes were measured between 200 and 300 nm using an AVIV 202SF spectropolarimeter (AVIV Biomedical) at 25°C, at a concentration of 5 mM, in phosphate-buffered saline.…”

Section: Itc and CD Spectroscopymentioning

confidence: 99%

Determination of the Structure and Catalytic Mechanism of Sorghum bicolor Caffeic Acid O-Methyltransferase and the Structural Impact of Three brown midrib12 Mutations

Green¹,

Lewis

Barr

et al. 2014

Plant Physiology

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Using S-adenosyl-methionine as the methyl donor, caffeic acid O-methyltransferase from sorghum (Sorghum bicolor; SbCOMT) methylates the 5-hydroxyl group of its preferred substrate, 5-hydroxyconiferaldehyde. In order to determine the mechanism of SbCOMT and understand the observed reduction in the lignin syringyl-to-guaiacyl ratio of three brown midrib12 mutants that carry COMT gene missense mutations, we determined the apo-form and S-adenosyl-methionine binary complex SbCOMT crystal structures and established the ternary complex structure with 5-hydroxyconiferaldehyde by molecular modeling. These structures revealed many features shared with monocot ryegrass (Lolium perenne) and dicot alfalfa (Medicago sativa) COMTs. SbCOMT steady-state kinetic and calorimetric data suggest a random bi-bi mechanism. Based on our structural, kinetic, and thermodynamic results, we propose that the observed reactivity hierarchy among 4,5-dihydroxy-3-methoxycinnamyl (and 3,4-dihydroxycinnamyl) aldehyde, alcohol, and acid substrates arises from the ability of the aldehyde to stabilize the anionic intermediate that results from deprotonation of the 5-hydroxyl group by histidine-267. Additionally, despite the presence of other phenylpropanoid substrates in vivo, sinapaldehyde is the preferential product, as demonstrated by its low K m for 5-hydroxyconiferaldehyde. Unlike its acid and alcohol substrates, the aldehydes exhibit product inhibition, and we propose that this is due to nonproductive binding of the S-cis-form of the aldehydes inhibiting productive binding of the S-trans-form. The S-cisaldehydes most likely act only as inhibitors, because the high rotational energy barrier around the 2-propenyl bond prevents S-trans-conversion, unlike alcohol substrates, whose low 2-propenyl bond rotational energy barrier enables rapid S-cis/S-transinterconversion.

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“…Gor is a glutathione reductase, involved in the generation of glutathione, which maintains the reducing environment of the cell (62). YqjG is glutathionyl hydroquinone reductase, which utilizes glutathione to reduce a wide range of organic molecules (38). HemE is a uroporphyrinogen decarboxylase involved in the biosynthesis of the heme group, which is an important cofactor for antioxidant enzymes like catalase and peroxidase (63).…”

Section: Discussionmentioning

confidence: 99%

“…Protein 3D Structure and Secondary Structure Prediction-All protein 3D structures were obtained from published studies (31)(32)(33)(34)(35)(36)(37)(38) and RCSB PDB (39), and visualized by RasMol software (40). We used the EcoGene 3.0 (41), which contained the QUARK prediction method (42), to predict the secondary structure of proteins without reported 3D structures.…”

Section: Methodsmentioning

confidence: 99%

Identification of 2-oxohistidine Interacting Proteins Using E. coli Proteome Chips

Lin

Tsai

Liu

et al. 2016

Molecular & Cellular Proteomics

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Cellular proteins are constantly damaged by reactive oxygen species generated by cellular respiration. Because of its metal-chelating property, the histidine residue is easily oxidized in the presence of Cu/Fe ions and H 2 O 2 via metal-catalyzed oxidation, usually converted to 2-oxohistidine. We hypothesized that cells may have evolved antioxidant defenses against the generation of 2-oxohistidine residues on proteins, and therefore there would be cellular proteins which specifically interact with this oxidized side chain. Using two chemically synthesized peptide probes containing 2-oxohistidine, high-throughput interactome screening was conducted using the E. coli K12 proteome microarray containing >4200 proteins. Ten interacting proteins were identified, and successfully validated using a third peptide probe, fluorescence polarization assays, as well as binding constant measurements. We discovered that 9 out of 10 identified proteins seemed to be involved in redox-related cellular functions. We also built the functional interaction network to reveal their interacting proteins. The network showed that our interacting proteins were enriched in oxido-reduction processes, ion binding, and carbon metabolism. A consensus motif was identified among these 10 bacterial interacting proteins based on bioinformatic analysis, which also appeared to be present on human S100A1 protein. Besides, we found that the consensus binding motif among our identified proteins, including bacteria and human, were located within ␣-helices and faced the outside of proteins. The combination of chemically engineered peptide probes with proteome microarrays proves to be an efficient discovery platform for protein interactomes of unusual post-translational modifications, and sensitive enough to detect even the insertion of a single oxygen atom in this case.

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Structural Understanding of the Glutathione-dependent Reduction Mechanism of Glutathionyl-Hydroquinone Reductases

Cited by 15 publications

References 24 publications

Trametes versicolor glutathione transferase Xi 3, a dual Cys‐GST with catalytic specificities of both Xi and Omega classes

Trametes versicolor glutathione transferase Xi 3, a dual Cys‐GST with catalytic specificities of both Xi and Omega classes

Determination of the Structure and Catalytic Mechanism of Sorghum bicolor Caffeic Acid O-Methyltransferase and the Structural Impact of Three brown midrib12 Mutations

Identification of 2-oxohistidine Interacting Proteins Using E. coli Proteome Chips

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