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ABSTRACT: Cyclic peptides with a linear tail (CPLT) have been successfully used to model two zinc fingers (ZFs) adopting the treble-clef- and loosened zinc-ribbon folds. In this article, we examine the factors that may influence the design of such ZF models: mutations in the sequence, size of the cycle, and size of the tail. For this purpose, several peptides derived from the CPLT-based models of the treble-clef- and loosened zinc-ribbon ZF were synthesized and studied. CPLT-based models appear to be robust toward mutations, accommodate various cycle sizes, and are sensible to the size of the linking region of the tail located between the cycle and the coordinating amino acids. Based on these criteria, we describe the design of a new CPLT-based model for the zinc-ribbon ZFs, L , and compare it to a linear analogue, L . The model complex Zn⋅L is able to fold correctly around the metal ion contrary to Zn⋅L , suggesting that CPLT-based models are more likely to yield structurally meaningful models of ZF sites than linear peptide models. Finally, we draw some rules that could allow the design of new CPLT-based metallopeptides with a controlled fold.
Chemistry 03/2013; 19(12):3921-31. · 5.93 Impact Factor
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ABSTRACT: A model of rubredoxin based on a cyclic peptide with a linear tail is presented. This model reproduces almost perfectly the fold, the spectroscopic characterizations and the redox activity of rubredoxins.
Chemical Communications 03/2013; · 6.17 Impact Factor
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ABSTRACT: Iron-sulfur (Fe-S) cluster-containing proteins are essential components of cells. In eukaryotes, Fe-S clusters are synthesized by the mitochondrial iron-sulfur cluster (ISC) machinery and the cytosolic iron-sulfur assembly (CIA) system. In the mammalian ISC machinery, pre-assembly of Fe-S cluster on the scaffold protein (ISCU) involves a cysteine desulfurase complex (NFS1/ISD11) and frataxin (FXN), the protein deficient in Freidreich's ataxia. Here we show, by comparing biochemical and spectroscopic properties of quaternary (ISCU/NFS1/ISD11/FXN) and ternary (ISCU/NFS1/ISD11) complexes, that FXN stabilizes the quaternary complex and controls iron entry to the complex through activation of cysteine desulfurization. Furthermore, we show for the first time that, in the presence of iron and L-cysteine, a [Fe4S4] cluster is formed within the quaternary complex that can be transferred to mammalian aconitase (mACO2) to generate an active enzyme. In the absence of FXN, although the ternary complex can assemble an Fe-S cluster, the cluster is inefficiently transferred to ACO2. Together, these data help further unravel the Fe-S cluster assembly process and the molecular basis of Friedreich's ataxia.
Journal of the American Chemical Society 12/2012; · 9.91 Impact Factor
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Phanelie Perche-Letuvee,
Velavan Kathirvelu,
Gustav Berggren,
Martin Clemancey, Jean-Marc Latour,
Vincent Maurel,
Thierry Douki,
Jean Armengaud,
Etienne Mulliez,
Marc Fontecave,
Ricardo Garcia-Serres,
Serge Gambarelli,
Mohamed Atta
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ABSTRACT: Wybutosine (yW) and its derivatives are found in position 37 of tRNA encoding Phe in eukaryotes and archaea. They are believed to play a key role in the decoding function of the ribosome. The second step in the biosynthesis of yW is catalyzed by TYW1 protein which is a member of the well-established class of metalloenzymes called Radical-SAM. These enzymes use a [4Fe-4S] cluster, chelated by three cysteines in a CysX3CysX2Cys motif, and S-Adenosyl-L-Methionine (SAM) to generate a 5-deoxyadenosyl radical that initiates various chemically challenging reactions. Sequence analysis of TYW1 proteins revealed, in the N-terminal half of the enzyme, beside the Radical-SAM cysteine triad an additional highly conserved cysteine motif. In this study we show by combining analytical and spectroscopic methods including UV-visible absorption, Mossbauer, EPR and HYSCORE spectroscopies that these additional cysteines are involved in the coordination of a second [4Fe-4S] cluster displaying a free coordination site able to bind pyruvate, the second substrate of the reaction. The presence of two distinct iron-sulfur clusters on TYW1 is reminiscent of MiaB, another tRNA-modifying metalloenzyme whose active form was shown to bind two iron-sulfur clusters. A possible role for the second [4Fe-4S] cluster in the enzyme activity is discussed.
Journal of Biological Chemistry 10/2012; · 4.77 Impact Factor
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Béatrice Py,
Catherine Gerez,
Sandra Angelini,
Rémy Planel,
Daniel Vinella,
Laurent Loiseau,
Emmanuel Talla,
Céline Brochier-Armanet,
Ricardo Garcia Serres, Jean-Marc Latour,
Sandrine Ollagnier-de Choudens,
Marc Fontecave,
Frédéric Barras
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ABSTRACT: Biosynthesis of iron-sulphur (Fe-S) proteins is catalysed by multi-protein systems, ISC and SUF. However, 'non-ISC, non-SUF' Fe-S biosynthesis factors have been described, both in prokaryotes and eukaryotes. Here we report in vitro and in vivo investigations of such a 'non-ISC, non SUF' component, the Nfu proteins. Phylogenomic analysis allowed us to define four subfamilies. Escherichia coli NfuA is within subfamily II. Most members of this subfamily have a Nfu domain fused to a 'degenerate' A-type carrier domain (ATC*) lacking Fe-S cluster co-ordinating Cys ligands. The Nfu domain binds a [4Fe-4S] cluster while the ATC* domain interacts with NuoG (a complex I subunit) and aconitase B (AcnB). In vitro, holo-NfuA promotes maturation of AcnB. In vivo, NfuA is necessary for full activity of complex I under aerobic growth conditions, and of AcnB in the presence of superoxide. NfuA receives Fe-S clusters from IscU/HscBA and SufBCD scaffolds and eventually transfers them to the ATCs IscA and SufA. This study provides significant information on one of the Fe-S biogenesis factors that has been often used as a building block by ISC and/or SUF synthesizing organisms, including bacteria, plants and animals.
Molecular Microbiology 09/2012; 86(1):155-71. · 5.01 Impact Factor
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ABSTRACT: Stop for NadA! A [4Fe-4S] enzyme, NadA, catalyzes the formation of quinolinic acid in de novo nicotinamide adenine dinucleotide (NAD) biosynthesis. A structural analogue of an intermediate, 4,5-dithiohydroxyphthalic acid (DTHPA), has an in vivo NAD biosynthesis inhibiting activity in E. coli. The inhibitory effect can be explained by the coordination of DTHPA thiolate groups to a unique Fe site of the NadA [4Fe-4S] cluster.
Angewandte Chemie International Edition 06/2012; 51(31):7711-4. · 13.45 Impact Factor
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ABSTRACT: The reactivity of a series of Zn(Cys)(4) zinc finger model peptides towards H(2)O(2) and O(2) has been investigated. The oxidation products were identified by HPLC and ESI-MS analysis. At pH<7.5, the zinc complexes and the free peptides are oxidised to bis-disulfide-containing peptides. Above pH 7.5, the oxidation of the zinc complexes by H(2)O(2) also yields sulfinate- and sulfonate-containing overoxidised peptides. At pH 7.0, monitoring of the reactions between the zinc complexes and H(2)O(2) by HPLC revealed the sequential formation of two disulfides. Several techniques for the determination of the rate constant for the first oxidation step corresponding to the attack of H(2)O(2) by the Zn(Cys)(4) site have been compared. This rate constant can be reliably determined by monitoring the oxidation by HPLC, fluorescence, circular dichroism or absorption spectroscopy in the presence of excess ethyleneglycol bis(2-aminoethyl ether)tetraacetic acid. In contrast, monitoring of the release of zinc with 4-(2-pyridylazo)resorcinol or of the thiol content with 5,5'-dithiobis(2-nitrobenzoate) did not yield reliable values of this rate constant for the case in which the formation of the second disulfide is slower than the formation of the first. The kinetic measurements clearly evidence a protective effect of zinc on the oxidation of the cysteines by both H(2)O(2) and O(2), which points to the fact that zinc binding diminishes the nucleophilicity of the thiolates. In addition, the reaction between the zinc finger and H(2)O(2) is too slow to consider zinc fingers as potential sensors for H(2)O(2) in cells.
Chemistry 11/2011; 17(49):13762-72. · 5.93 Impact Factor
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Eric Gouré,
Grégory Thiabaud,
Michaël Carboni,
Nathalie Gon,
Patrick Dubourdeaux,
Ricardo Garcia-Serres,
Martin Clémancey,
Jean-Louis Oddou,
Adeline Y Robin,
Lilian Jacquamet,
Lionel Dubois,
Geneviève Blondin, Jean-Marc Latour
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ABSTRACT: The coupling of electron and proton transfers is currently under intense scrutiny. This Communication reports a new kind of proton-coupled electron transfer within a homodinuclear first-row transition-metal complex. The triply-bridged complex [Fe(III)(μ-OPh)(μ(2)-mpdp)Fe(II)(NH(2)Bn)] (1; mpdp(2-) = m-phenylenedipropionate) bearing a terminal aminobenzyl ligand can be reversibly deprotonated to the anilinate complex 2 whose core [Fe(II)(μ-OPh)(μ(2)-mpdp)Fe(III)(NHBn)] features an inversion of the iron valences. This observation is supported by a combination of UV-visible, (1)H NMR, and Mössbauer spectroscopic studies.
Inorganic Chemistry 06/2011; 50(14):6408-10. · 4.60 Impact Factor
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ABSTRACT: Progress in understanding the mechanism underlying the enzymatic formation of iron-sulfur clusters is difficult since it involves a complex reaction and a multi-component system. By exploiting different spectroscopies, we characterize the effect on the enzymatic kinetics of cluster formation of CyaY, the bacterial ortholog of frataxin, on cluster formation on the scaffold protein IscU. Frataxin/CyaY is a highly conserved protein implicated in an incurable ataxia in humans. Previous studies had suggested a role of CyaY as an inhibitor of iron sulfur cluster formation. Similar studies on the eukaryotic proteins have however suggested for frataxin a role as an activator. Our studies independently confirm that CyaY slows down the reaction and shed new light onto the mechanism by which CyaY works. We observe that the presence of CyaY does not alter the relative ratio between [2Fe2S](2+) and [4Fe4S](2+) but directly affects enzymatic activity.
PLoS ONE 01/2011; 6(7):e21992. · 4.09 Impact Factor
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ABSTRACT: Zinc fingers are ubiquitous small protein domains which have a Zn(Cys)(4-x)(His)(x) site. They possess great diversity in their structure and amino acid composition. Using a family of six peptides, it was possible to assess the influence of hydrophobic amino acids on the metal-peptide affinities and on the rates of metal association and dissociation. A model of a treble-clef zinc finger, a model of the zinc finger site of a redox-switch protein, and four variants of the classical ββα zinc finger were used. They differ in their coordination set, their sequence length, and their hydrophobic amino acid content. The speciation, metal binding constants, and structure of these peptides have been investigated as a function of pH. The zinc binding constants of peptides, which adopt a well-defined structure, were found to be around 10(15) at pH 7.0. The rates of zinc exchange between EDTA and the peptides were also assessed. We evidenced that the packing of hydrophobic amino acids into a well-defined hydrophobic core can have a drastic influence on both the binding constant and the kinetics of metal exchange. Notably, well-packed hydrophobic amino acids can increase the stability constant by 4 orders of magnitude. The half-life of zinc exchange was also seen to vary significantly depending on the sequence of the zinc finger. The possible causes for this behavior are discussed. This work will help in understanding the dynamics of zinc exchange in zinc-containing proteins.
Journal of the American Chemical Society 12/2010; 132(50):17760-74. · 9.91 Impact Factor
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ABSTRACT: Assembly of iron-sulfur (Fe-S) clusters and maturation of Fe-S proteins in vivo require complex machineries. In Escherichia coli, under adverse stress conditions, this process is achieved by the SUF system that contains six proteins as follows: SufA,
SufB, SufC, SufD, SufS, and SufE. Here, we provide a detailed characterization of the SufBCD complex whose function was so
far unknown. Using biochemical and spectroscopic analyses, we demonstrate the following: (i) the complex as isolated exists
mainly in a 1:2:1 (B:C:D) stoichiometry; (ii) the complex can assemble a [4Fe-4S] cluster in vitro and transfer it to target proteins; and (iii) the complex binds one molecule of flavin adenine nucleotide per SufBC2D complex, only in its reduced form (FADH2), which has the ability to reduce ferric iron. These results suggest that the SufBC2D complex functions as a novel type of scaffold protein that assembles an Fe-S cluster through the mobilization of sulfur
from the SufSE cysteine desulfurase and the FADH2-dependent reductive mobilization of iron.
Journal of Biological Chemistry 07/2010; 285(30):23331-23341. · 4.77 Impact Factor
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ABSTRACT: Assembly of iron-sulfur (Fe-S) clusters and maturation of Fe-S proteins in vivo require complex machineries. In Escherichia coli, under adverse stress conditions, this process is achieved by the SUF system that contains six proteins as follows: SufA, SufB, SufC, SufD, SufS, and SufE. Here, we provide a detailed characterization of the SufBCD complex whose function was so far unknown. Using biochemical and spectroscopic analyses, we demonstrate the following: (i) the complex as isolated exists mainly in a 1:2:1 (B:C:D) stoichiometry; (ii) the complex can assemble a [4Fe-4S] cluster in vitro and transfer it to target proteins; and (iii) the complex binds one molecule of flavin adenine nucleotide per SufBC(2)D complex, only in its reduced form (FADH(2)), which has the ability to reduce ferric iron. These results suggest that the SufBC(2)D complex functions as a novel type of scaffold protein that assembles an Fe-S cluster through the mobilization of sulfur from the SufSE cysteine desulfurase and the FADH(2)-dependent reductive mobilization of iron.
Journal of Biological Chemistry 05/2010; 285(30):23331-41. · 4.77 Impact Factor
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Mariappan Murali,
Sanjit Nayak,
José Sánchez Costa,
Joan Ribas,
Ilpo Mutikainen,
Urho Turpeinen,
Martin Clémancey,
Ricardo Garcia-Serres, Jean-Marc Latour,
Patrick Gamez,
Geneviève Blondin,
Jan Reedijk
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ABSTRACT: The aerobic reaction of the Schiff-base ligand N-(benzimidazol-2-yl)salicylaldimine (Hbisi) with iron(II) perchlorate in methanol leads to the formation of the remarkable coordination compound [Fe(4)(mu(4)-O)(mu-MeO)(4)(bisi)(4)](ClO(4))(2) x 4 MeOH (1), whose single-crystal X-ray structure reveals the presence of a discrete Fe(III)(4)(mu(4)-O) core. Magnetic and Mossbauer studies both show that the exchange interaction within the square tetranuclear iron(III) unit is dominated by the central bridging mu(4)-oxido ligand, the involvement of the mu-methoxido bridges being negligible.
Inorganic Chemistry 03/2010; 49(5):2427-34. · 4.60 Impact Factor
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Simon Arragain,
Ricardo Garcia-Serres,
Geneviève Blondin,
Thierry Douki,
Martin Clemancey, Jean-Marc Latour,
Farhad Forouhar,
Helen Neely,
Gaetano T. Montelione,
John F. Hunt,
Etienne Mulliez,
Marc Fontecave,
Mohamed Atta
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ABSTRACT: Post-translational modifications of ribosomal proteins are important for the accuracy of the decoding machinery. A recent
in vivo study has shown that the rimO gene is involved in generation of the 3-methylthio derivative of residue Asp-89 in ribosomal protein S12 (Anton, B. P., Saleh,
L., Benner, J. S., Raleigh, E. A., Kasif, S., and Roberts, R. J. (2008) Proc. Natl. Acad. Sci. U. S. A. 105, 1826–1831). This reaction is formally identical to that catalyzed by MiaB on the C2 of adenosine 37 near the anticodon
of several tRNAs. We present spectroscopic evidence that Thermotoga maritima RimO, like MiaB, contains two [4Fe-4S] centers, one presumably bound to three invariant cysteines in the central radical
S-adenosylmethionine (AdoMet) domain and the other to three invariant cysteines in the N-terminal UPF0004 domain. We demonstrate
that holo-RimO can specifically methylthiolate the aspartate residue of a 20-mer peptide derived from S12, yielding a mixture
of mono- and bismethylthio derivatives. Finally, we present the 2.0 Å crystal structure of the central radical AdoMet and
the C-terminal TRAM (tRNA methyltransferase 2 and MiaB) domains in apo-RimO. Although the core of the open triose-phosphate isomerase (TIM) barrel of the radical AdoMet domain
was conserved, RimO showed differences in domain organization compared with other radical AdoMet enzymes. The unusually acidic
TRAM domain, likely to bind the basic S12 protein, is located at the distal edge of the radical AdoMet domain. The basic S12
protein substrate is likely to bind RimO through interactions with both the TRAM domain and the concave surface of the incomplete
TIM barrel. These biophysical results provide a foundation for understanding the mechanism of methylthioation by radical AdoMet
enzymes in the MiaB/RimO family.
Journal of Biological Chemistry 02/2010; 285(8):5792-5801. · 4.77 Impact Factor
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ABSTRACT: Bacteria adapt to elevated levels of reactive oxygen species (ROS) by increasing the expression of detoxification enzymes and repair proteins. These defences are regulated by transcription factors that activate specific genes in response to ROS. In Bacillus subtilis, the adaptive response to peroxide stress is mainly under control of three proteins: sigma(B), PerR and OhrR. sigma(B) is a general stress response transcription factor. PerR is a dimeric zinc protein with a regulatory site that coordinates either a Fe(2+) or a Mn(2+) metal ion. In the presence of iron, PerR mediates strong induction of the perR regulon in response to hydrogen peroxide (H(2)O(2)). In contrast to PerR, the OhrR protein is weakly activated by H(2)O(2) but it shows a much higher reactivity for organic hydroperoxides. OhrR controls the expression of a thiol-dependent peroxidase that reduces organic hydroperoxides into their corresponding alcohols. In this review we emphasis peroxide sensing mechanisms for both proteins, focusing on recent biochemical and structural data.
Molecular BioSystems 02/2010; 6(2):316-23. · 3.53 Impact Factor
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Simon Arragain,
Ricardo Garcia-Serres,
Geneviève Blondin,
Thierry Douki,
Martin Clemancey, Jean-Marc Latour,
Farhad Forouhar,
Helen Neely,
Gaetano T Montelione,
John F Hunt,
Etienne Mulliez,
Marc Fontecave,
Mohamed Atta
[show abstract]
[hide abstract]
ABSTRACT: Post-translational modifications of ribosomal proteins are important for the accuracy of the decoding machinery. A recent in vivo study has shown that the rimO gene is involved in generation of the 3-methylthio derivative of residue Asp-89 in ribosomal protein S12 (Anton, B. P., Saleh, L., Benner, J. S., Raleigh, E. A., Kasif, S., and Roberts, R. J. (2008) Proc. Natl. Acad. Sci. U. S. A. 105, 1826–1831). This reaction is formally identical to that catalyzed by MiaB on the C2 of adenosine 37 near the anticodon of several tRNAs. We present spectroscopic evidence that Thermotoga maritima RimO, like MiaB, contains two [4Fe-4S] centers, one presumably bound to three invariant cysteines in the central radical S-adenosylmethionine (AdoMet) domain and the other to three invariant cysteines in the N-terminal UPF0004 domain. We demonstrate that holo-RimO can specifically methylthiolate the aspartate residue of a 20-mer peptide derived from S12, yielding a mixture of mono- and bismethylthio derivatives. Finally, we present the 2.0 Å crystal structure of the central radical AdoMet and the C-terminal TRAM (tRNA methyltransferase 2 and MiaB) domains in apo-RimO. Although the core of the open triose-phosphate isomerase (TIM) barrel of the radical AdoMet domain was conserved, RimO showed differences in domain organization compared with other radical AdoMet enzymes. The unusually acidic TRAM domain, likely to bind the basic S12 protein, is located at the distal edge of the radical AdoMet domain. The basic S12 protein substrate is likely to bind RimO through interactions with both the TRAM domain and the concave surface of the incomplete TIM barrel. These biophysical results provide a foundation for understanding the mechanism of methylthioation by radical AdoMet enzymes in the MiaB/RimO family.
Journal of Biological Chemistry 12/2009; · 4.77 Impact Factor
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ABSTRACT: Two peptides, L(TC) and L(TC)(T) have been synthesised to model the treble-clef zinc fingers encountered in many Zn(Cys)(4)-site-containing proteins. Both are cyclic peptides with a linear tail grafted on a glutamate side chain of the cycle. They differ by the length of this tail, which lacks five amino acids in L(TC)(T) compared to L(TC). Both peptides bind Zn(2+) and Co(2+) in 1:1 metal/peptide ratio and the structure of these complexes have been characterised by NMR, UV/Vis and CD spectroscopy. Both peptides fold the same way around the metal ion and they fully reproduce the classical fold of treble-clef zinc fingers and display an extended hydrogen-bond network around the coordinating sulfur atoms. The structures of the ML(TC) complexes reveal that the linear tail forms a short two-turn alpha-helix, present in the metallated form only. The formation of this helix constitutes a rare example of metal-induced folding. The second turn of this helix is composed of the five amino acids that are absent in L(TC)(T). The study of the pH-dependence of the Zn(2+) binding constants shows that the metal ion is bound by four cysteinates above pH 5.2 and the binding constants are the highest reported so far. Interestingly, the binding constant of Zn x L(TC) is about tenfold higher than that of Zn x L(TC)(T). This difference clearly indicates that the helix, present in Zn x L(TC) only, stabilises the Zn(2+) complex by about 1.2 kcal mol(-1). The origin of this stabilisation is ascribed to an electrostatic interaction between the [ZnS(4)](2-) centre and the helix. This reveals a cooperative effect: zinc binding allows the folding of the tail into a helix which, in turn, strengthens the zinc complex.
Chemistry 05/2009; 15(19):4798-810. · 5.93 Impact Factor
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Daouda A K Traoré,
Abdelnasser El Ghazouani,
Lilian Jacquamet,
Franck Borel,
Jean-Luc Ferrer,
David Lascoux,
Jean-Luc Ravanat,
Michel Jaquinod,
Geneviève Blondin,
Christelle Caux-Thang,
Victor Duarte, Jean-Marc Latour
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ABSTRACT: In Bacillus subtilis, PerR is a metal-dependent sensor of hydrogen peroxide. PerR is a dimeric zinc protein with a regulatory site that coordinates either Fe(2+) (PerR-Zn-Fe) or Mn(2+) (PerR-Zn-Mn). Though most of the peroxide sensors use cysteines to detect H(2)O(2), it has been shown that reaction of PerR-Zn-Fe with H(2)O(2) leads to the oxidation of one histidine residue. Oxidation of PerR leads to the incorporation of one oxygen atom into His37 or His91. This study presents the crystal structure of the oxidized PerR protein (PerR-Zn-ox), which clearly shows a 2-oxo-histidine residue in position 37. Formation of 2-oxo-histidine is demonstrated and quantified by HPLC-MS/MS. EPR experiments indicate that PerR-Zn-H37ox retains a significant affinity for the regulatory metal, whereas PerR-Zn-H91ox shows a considerably reduced affinity for the metal ion. In spite of these major differences in terms of metal binding affinity, oxidation of His37 and/or His91 in PerR prevents DNA binding.
Nature Chemical Biology 01/2009; 5(1):53-9. · 14.69 Impact Factor
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Daouda A K Traor|[eacute,
Abdelnasser El Ghazouani,
Lilian Jacquamet,
Franck Borel,
Jean-Luc Ferrer,
David Lascoux,
Jean-Luc Ravanat,
Michel Jaquinod,
Genevi|[egrave]|ve Blondin,
Christelle Caux-Thang,
Victor Duarte, Jean-Marc Latour
[show abstract]
[hide abstract]
ABSTRACT: In Bacillus subtilis, PerR is a metal-dependent sensor of hydrogen peroxide. PerR is a dimeric zinc protein with a regulatory site that coordinates either Fe2+ (PerR-Zn-Fe) or Mn2+ (PerR-Zn-Mn). Though most of the peroxide sensors use cysteines to detect H2O2, it has been shown that reaction of PerR-Zn-Fe with H2O2 leads to the oxidation of one histidine residue. Oxidation of PerR leads to the incorporation of one oxygen atom into His37 or His91. This study presents the crystal structure of the oxidized PerR protein (PerR-Zn-ox), which clearly shows a 2-oxo-histidine residue in position 37. Formation of 2-oxo-histidine is demonstrated and quantified by HPLC-MS/MS. EPR experiments indicate that PerR-Zn-H37ox retains a significant affinity for the regulatory metal, whereas PerR-Zn-H91ox shows a considerably reduced affinity for the metal ion. In spite of these major differences in terms of metal binding affinity, oxidation of His37 and/or His91 in PerR prevents DNA binding.
Nature Chemical Biology 12/2008; 5(1):53-59. · 14.69 Impact Factor
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Angewandte Chemie International Edition 02/2008; 47(4):715-7. · 13.45 Impact Factor
