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Loïc Mathieu,
Baptiste Legrand,
Cheng Deng,
Lubomir Vezenkov,
Emmanuel Wenger, Claude Didierjean,
Muriel Amblard,
Marie-Christine Averlant-Petit,
Nicolas Masurier,
Vincent Lisowski,
Jean Martinez,
Ludovic T Maillard
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ABSTRACT: 9-Helix: 4-Amino(methyl)-1,3-thiazole-5-carboxylic acids (ATCs) were synthesized as new γ-amino acid building blocks. The structures of various ATC oligomers were analyzed in solution by CD and NMR spectroscopy and in the solid state by X-ray crystallography. The ATC sequences adopted a well-defined 9-helix structure in the solid state and in aprotic and protic organic solvents as well as in aqueous solution.
Angewandte Chemie International Edition 04/2013; · 13.45 Impact Factor
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ABSTRACT: SpLigG is one of the three glutathione transferases (GSTs) involved in the process of lignin breakdown in the soil bacterium Sphingobium sp. SYK-6. Sequence comparisons showed that SpLigG and several proteobacteria homologues form an independent cluster within cysteine-containing GSTs. The relationship between SpLigG and other GSTs was investigated. The X-ray structure and biochemical properties of SpLigG indicate that this enzyme belongs to the omega class of glutathione transferases. However, the hydrophilic substrate binding site of SpLigG, together with its known ability to stereoselectively deglutathionylate the physiological substrate α-glutathionyl-β-hydroxypropiovanillone, argues for broadening the definition of the omega class. STRUCTURED SUMMARY OF PROTEIN INTERACTIONS: SpLigG and SpLigGbind by X-ray crystallography (View interaction).
FEBS letters 10/2012; · 3.54 Impact Factor
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ABSTRACT: BAC for more: A constrained bicyclic building block with urea linkages is an efficient combination for the formation of a highly rigid helical system. This type of bicyclic amino carbamoyl (BAC) foldamer was studied both in solution and in the solid state. A robust H-bond (dotted line) network was found between the carbonyl oxygen atoms (red) and the amino groups (dark blue) within the helix.
Angewandte Chemie International Edition 10/2012; · 13.45 Impact Factor
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ABSTRACT: Structural dynamics associated with cofactor binding have been shown to play key roles in the catalytic mechanism of hydrolytic NAD(P)-dependent aldehyde dehydrogenases (ALDH). By contrast, no information is available for their CoA-dependent counterparts. We present here the first crystal structure of a CoA-dependent ALDH. The structure of the methylmalonate semialdehyde dehydrogenase (MSDH) from Bacillus subtilis in binary complex with NAD(+) shows that, in contrast to what is observed for hydrolytic ALDHs, the nicotinamide ring is well defined in the electron density due to direct and H(2)O-mediated hydrogen bonds with the carboxamide. The structure also reveals that a conformational isomerization of the NMNH is possible in MSDH, as shown for hydrolytic ALDHs. Finally, the adenine ring is substantially more solvent-exposed, a result that could be explained by the presence of a Val residue at position 229 in helix α(F) that reduces the depth of the binding pocket and the absence of Gly-225 at the N-terminal end of helix α(F). Substitution of glycine for Val-229 and/or insertion of a glycine residue at position 225 resulted in a significant decrease of the rate constant associated with the dissociation of NADH from the NADH/thioacylenzyme complex, thus demonstrating that the weaker stabilization of the adenine ring is a key factor in triggering the early NADH release in the MSDH-catalyzed reaction. This study provides for the first time structural insights into the mechanism whereby the cofactor binding mode is responsible at least in part for the different kinetic behaviors of the hydrolytic and CoA-dependent ALDHs.
Journal of Biological Chemistry 07/2012; 287(37):31095-103. · 4.77 Impact Factor
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ABSTRACT: In order to investigate the ability of the (S)-aminobicyclo[2.2.2]octane-2-carboxylic acid 1 (H-(S)-ABOC-OH) to induce reverse turns into peptides, two model tripeptides, in which this bicyclic unit was incorporated into the second position, were synthesized and analyzed by FT-IR, CD, NMR, and X-ray studies.
Organic Letters 02/2012; 14(4):960-3. · 5.86 Impact Factor
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Aik-Hong Teh,
Jennifer A Saito,
Aida Baharuddin,
Jason R Tuckerman,
James S Newhouse,
Masaomi Kanbe,
Elizabeth I Newhouse,
Rashidah Abdul Rahim,
Frédérique Favier, Claude Didierjean,
Eduardo H S Sousa,
Matthew B Stott,
Peter F Dunfield,
Gonzalo Gonzalez,
Marie-Alda Gilles-Gonzalez,
Nazalan Najimudin,
Maqsudul Alam
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ABSTRACT: Hell's Gate globin I (HGbI), a heme-containing protein structurally homologous to mammalian neuroglobins, has been identified from an acidophilic and thermophilic obligate methanotroph, Methylacidiphilum infernorum. HGbI has very high affinity for O(2) and shows barely detectable autoxidation in the pH range of 5.2-8.6 and temperature range of 25-50°C. Examination of the heme pocket by X-ray crystallography and molecular dynamics showed that conformational movements of Tyr29(B10) and Gln50(E7), as well as structural flexibility of the GH loop and H-helix, may play a role in modulating its ligand binding behavior. Bacterial HGbI's unique resistance to the sort of extreme acidity that would extract heme from any other hemoglobin makes it an ideal candidate for comparative structure-function studies of the expanding globin superfamily.
FEBS letters 09/2011; 585(20):3250-8. · 3.54 Impact Factor
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ABSTRACT: The asymmetric Friedel-Crafts alkylation of various indoles with a chiral nitroacrylate provides optically active β-tryptophan analogues after reduction of the nitro group and removal of the chiral auxiliary. This reaction generally occurs in good yield and high diastereoselectivity (up to 90:10).
The Journal of Organic Chemistry 06/2011; 76(15):6116-24. · 4.45 Impact Factor
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Jérémy Couturier,
Elke Ströher,
Angela-Nadia Albetel,
Thomas Roret,
Meenakumari Muthuramalingam,
Lionel Tarrago,
Thorsten Seidel,
Pascale Tsan,
Jean-Pierre Jacquot,
Michael K Johnson,
Karl-Josef Dietz, Claude Didierjean,
Nicolas Rouhier
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ABSTRACT: Unlike thioredoxins, glutaredoxins are involved in iron-sulfur cluster assembly and in reduction of specific disulfides (i.e. protein-glutathione adducts), and thus they are also important redox regulators of chloroplast metabolism. Using GFP fusion, AtGrxC5 isoform, present exclusively in Brassicaceae, was shown to be localized in chloroplasts. A comparison of the biochemical, structural, and spectroscopic properties of Arabidopsis GrxC5 (WCSYC active site) with poplar GrxS12 (WCSYS active site), a chloroplastic paralog, indicated that, contrary to the solely apomonomeric GrxS12 isoform, AtGrxC5 exists as two forms when expressed in Escherichia coli. The monomeric apoprotein possesses deglutathionylation activity mediating the recycling of plastidial methionine sulfoxide reductase B1 and peroxiredoxin IIE, whereas the dimeric holoprotein incorporates a [2Fe-2S] cluster. Site-directed mutagenesis experiments and resolution of the x-ray crystal structure of AtGrxC5 in its holoform revealed that, although not involved in its ligation, the presence of the second active site cysteine (Cys(32)) is required for cluster formation. In addition, thiol titrations, fluorescence measurements, and mass spectrometry analyses showed that, despite the presence of a dithiol active site, AtGrxC5 does not form any inter- or intramolecular disulfide bond and that its activity exclusively relies on a monothiol mechanism.
Journal of Biological Chemistry 06/2011; 286(31):27515-27. · 4.77 Impact Factor
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ABSTRACT: 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.
Journal of Biological Chemistry 03/2011; 286(11):9162-9173. · 4.77 Impact Factor
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ABSTRACT: A new N-Boc-protected monomer for the synthesis of oligourea foldamers containing the (1H-imidazolyl-4yl)methyl side chain of histidine, has been prepared in seven steps from Trt-His(τ-Trt)-OMe. This protecting group combination on histidine was found to be critical to ensure efficient access to the requisite activated building block. This new derivative, suitable for solid phase synthesis, expands the current arsenal of building blocks with proteinogenic side chains useful for the design of peptidomimetic oligourea foldamers.
Tetrahedron 01/2011; · 3.03 Impact Factor
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ABSTRACT: 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.
Journal of Biological Chemistry 12/2010; 286(11):9162-73. · 4.77 Impact Factor
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ABSTRACT: In order to gather biochemical information about class III glutaredoxins (CCxC/S active sites), the active sites of two poplar class I glutaredoxins, GrxC1 and C4, CGYC and CPYC, respectively, were transformed into CCMC or CCMS. All the recombinant mutated proteins bind [2Fe-2S] centers into holodimers, whereas monomeric apoforms possess glutathione-dependent reductase activity. The functionally important, hydrophobic GALWL C-terminal end, found in most class III glutaredoxins, prevents expression in Escherichia coli. Changing the C-terminal end of GrxS7.2, a genuine class III glutaredoxin, allowed purifying some holoproteins. These properties are discussed considering the documented function of class III glutaredoxins in development.
Biochemical and Biophysical Research Communications 12/2010; 403(3-4):435-41. · 2.48 Impact Factor
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ABSTRACT: The chiral β-nitroacrylate 2 derived from the (R)- or (S)-4-(3-hydroxy-4,4-dimethyl-2-oxopyrrolidin-1-yl) benzoic acid 1 acts as a reactive dienophile in a diastereoselective Diels-Alder reaction with 1,3-cyclohexadiene. The major cycloadducts have been isolated and transformed into enantiopure trans(2S,3S)- or (2R,3R)-N-Boc-3-aminobicyclic[2,2,2]octane-2-carboxylic acids 5. The trans-(2S,3S)- or (2R,3R)-N-Boc 3-(hydoxymethyl)-2-aminobicyclic[2,2,2]octane 6 derivatives were also obtained.
Chirality 10/2010; 23(3):245-9. · 2.35 Impact Factor
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ABSTRACT: The crystal structure of the title compound, C(16)H(23)N(3)O(4).CH(3)CN, was refined using a multipolar atom model transferred from an experimental electron-density database. The refinement showed some improvement in crystallographic statistical indices compared with the independent atom model. The triazepane ring adopts a twist-boat conformation. In the crystal structure, the molecule forms intermolecular contacts with 14 different neighbours. There are two N-H...O and one C-H...O intermolecular hydrogen bond.
Acta crystallographica. Section C, Crystal structure communications 06/2010; 66(Pt 6):o292-4. · 0.78 Impact Factor
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Angewandte Chemie International Edition 02/2010; 49(6):1067-70. · 13.45 Impact Factor
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Jeremy Couturier,
Cha San Koh,
Mirko Zaffagnini,
Alison M Winger,
Jose Manuel Gualberto,
Catherine Corbier,
Paulette Decottignies,
Jean-Pierre Jacquot,
Stéphane D Lemaire, Claude Didierjean,
Nicolas Rouhier
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ABSTRACT: Glutaredoxins (Grxs) are efficient catalysts for the reduction of mixed disulfides in glutathionylated proteins, using glutathione or thioredoxin reductases for their regeneration. Using GFP fusion, we have shown that poplar GrxS12, which possesses a monothiol (28)WCSYS(32) active site, is localized in chloroplasts. In the presence of reduced glutathione, the recombinant protein is able to reduce in vitro substrates, such as hydroxyethyldisulfide and dehydroascorbate, and to regenerate the glutathionylated glyceraldehyde-3-phosphate dehydrogenase. Although the protein possesses two conserved cysteines, it is functioning through a monothiol mechanism, the conserved C terminus cysteine (Cys(87)) being dispensable, since the C87S variant is fully active in all activity assays. Biochemical and crystallographic studies revealed that Cys(87) exhibits a certain reactivity, since its pK(a) is around 5.6. Coupled with thiol titration, fluorescence, and mass spectrometry analyses, the resolution of poplar GrxS12 x-ray crystal structure shows that the only oxidation state is a glutathionylated derivative of the active site cysteine (Cys(29)) and that the enzyme does not form inter- or intramolecular disulfides. Contrary to some plant Grxs, GrxS12 does not incorporate an iron-sulfur cluster in its wild-type form, but when the active site is mutated into YCSYS, it binds a [2Fe-2S] cluster, indicating that the single Trp residue prevents this incorporation.
Journal of Biological Chemistry 02/2009; 284(14):9299-310. · 4.77 Impact Factor
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Advances in experimental medicine and biology 02/2009; 611:201-2. · 1.09 Impact Factor
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Advances in experimental medicine and biology 02/2009; 611:39-40. · 1.09 Impact Factor
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ABSTRACT: The perfect blend: A new class of self-assembling cyclooligomers with mixed urea/amide backbone is described (see figure). A high level of hierarchical and directional control is achieved: depending on the level of backbone preorganization, columnar or tubular arrangements with either parallel or antiparallel growing modes can be selected.
Angewandte Chemie International Edition 02/2009; 48(9):1625-8. · 13.45 Impact Factor
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ABSTRACT: In order to determine the structural consequences of the Nx/CxH exchange in aza-peptides, we have solved the crystal molecular structures of some derivatives containing the aza-analogue of asparagine [Z-AzAsn(Me)-NMe2 (1), Z-AzAsn(Me)-Pro-NHiPr (2) and Piv-Pro-AzAsn(Me)-NHiPr (5), aspartic acid [Z-AzAsp(OEt)-Pro-NHiPr (3) and alanine (Boc-AzAla-Pro-NHiPr (4), by using X-ray diffraction. They reveal that the -nitrogen accommodates a pyramidal (1–4) or planar (5) structure depending on the sequence. When pyramidal, the -nitrogen assumes the R (D-like) chiralily. All of the derivatives but 1 adopt either a β1-folded (2–4) or βII-folded (5) structure in which the (AzAsn)NδH bond is intramolecularly hydrogen-bonded to the -nitrogen. © Munksgaard 1997.
European Journal of Allergy and Clinical Immunology 01/2009; 49(6):556 - 562. · 1.30 Impact Factor
