Mohamed A. Abdallah

University of Strasbourg, Strasburg, Alsace, France

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Publications (66)160.78 Total impact

  • Adel Zamri · Finton Sirockin · Mohamed A. Abdallah

    No preview · Article · Aug 2010 · ChemInform
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    ABSTRACT: The protective effect of pyoverdins Pa A and Pf, peptidic siderophores secreted respectively by Pseudomonas aeruginosa and fluorescens, was studied in primary cultures of human hepatocytes exposed to iron (50 or 100 μM of iron-citrate). AST, ALT and MDA releases were measured as indexes of cytotoxicity. In order to demonstrate that these chelators were able to decrease iron uptake or increase iron release from the hepatocytes, labelled cells were obtained by maintaining the cultures in the presence of 1 μM 55Fe ferric chloride plus 50 μM iron citrate. One day after iron treatment, an increase in AST, ALT and MDA release was observed with 50 or 100 μM of iron citrate; it appeared that the concentrations 50 and 100 μM of iron were highly toxic for human hepatocytes. In the presence of 50 or 100 μM of iron, the addition of 50 or 100 μM of Pa A or Pf was effective to inhibit the increase observed in the enzyme leakage and the MDA production resulting from iron exposure. In human hepatocytes cultured for 1 day in the presence of 1 μM 55Fe-50 μM iron citrate plus 50 or 100 μM Pa A or Pf, a net decrease of iron uptake by the cells was observed, as demonstrated by the low intracellular iron level. When the hepatocytes were cultured for 1 day in the presence of 1 μM 55Fe-50 μM iron citrate and then for a further day in the presence of 50 or 100 μM Pa A or Pf without additional iron, the chelators increased the extracellular iron level, indicating their iron release from the loaded cells; however, the effects of Pa A and Pf on iron release did not differ significantly. In conclusion, iron loading achieved by adding iron citrate to the culture medium is highly toxic for human hepatocytes. Pyoverdins Pa A and Pf are effective in protecting human hepatocytes against the toxic effect of iron by both decreasing the uptake of the metal and increasing its release from the loaded cells.
    No preview · Article · Dec 2008 · Liver International
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    ABSTRACT: The analogues of the coenzyme NADP+, nicotinamide–8-bromo-adenine dinucleotide phosphate (Nbr8ADP+) and 3-iodopyridine–adenine dinucleotide phosphate (io3PdADP+), were prepared. Nbr8ADP+ was found to be active in the hydrogen transfer and io3PdADP+ is a coenzyme competitive inhibitor for 6-phosphogluconate dehydrogenase. The binding of NADP+, NADPH and NADPH together with 6-phosphogluconate as well as that of both analogues to crystals of the enzyme 6-phosphogluconate dehydrogenase has been investigated at 0.6-nm resolution using difference electron density maps. The molecules bind in a similar position in a cleft in the enzyme subunit distant from the dimer interface. The orientation of the coenzyme in the site has been determined from the io3PdADP+–NADP+ difference density. The ternary complex difference density extends beyond that of the nicotinamide moiety of the coenzyme and tentatively indicates substrate binding. No clear identification of the bromine atom of Nbr8ADP+ can be made. However, the analogue is bound more deeply in the cleft than is NADP+. The NADPH density is the most clearly defined and has thus been used to fit a molecular model using an interactive graphics system, checking for preferred geometry. A possible conformation is presented which is significantly different from that of NAD+ in the lactate dehydrogenase ternary complex.
    Full-text · Article · Jun 2008
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    ABSTRACT: Under iron-deficient conditions, the Gram-negative bacterium Pseudomonas aeruginosa ATCC 15692 secretes a peptidic siderophore, pyoverdine PvdI, composed of an aromatic chromophore derived from 2,3-diamino-6,7-dihydroxyquinoline and a partially cyclized octapeptide, d-Ser- l-Arg- d-Ser- l-FoOHOrn-( l-Lys- l-FoOHOrn- l-Thr- l-Thr), in which the C-terminal carboxyl group forms a peptidic bond with the primary amine of the l-Lys side chain. In aqueous solution at room temperature, the (1)H NMR spectrum of pyoverdine PvdI-Ga(III) showed clear evidence of exchange broadening. At 253 K, two distinct conformations were observed and the measurement of structural constraints was possible. The three-dimensional structures of the two PvdI-Ga(III) conformers were determined, and analysis of the structures indicates that the observed conformational exchange involves a stereoisomerization of the metal binding coordination accompanied by a change in the global shape of the siderophore. This conformational transition was further characterized by heteronuclear relaxation experiments. The possible implications of this dynamic behavior for siderophore recognition by the receptor FpvAI are discussed.
    Full-text · Article · Apr 2008 · Biochemistry
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    ABSTRACT: Using synthetic functionalized analogues of pyochelin, a siderophore common to several pathogenic Pseudomonas and Burkholderia species, four fluoroquinolone-pyochelin conjugates were efficiently synthesized and evaluated for their biological activities.
    No preview · Article · Mar 2007 · Bioorganic & Medicinal Chemistry Letters
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    ABSTRACT: Using synthetic functionalized analogues of pyochelin, a siderophore common to several pathogenic Pseudomonas and Burkholderia species, four fluoroquinolone-pyochelin conjugates were efficiently synthesized and evaluated for their biological activities.
    No preview · Article · Feb 2007
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    ABSTRACT: Pyochelin, its analog 3''-nor-NH-pyochelin, and the related methyl hydroxamate, 2-(2'-hydroxyphenyl)-4,5-dihydrothiazol-4-carboxylic acid methoxymethyl amide, have been prepared together with their Fe(III) complexes. The solution stoichiometry and the coordination of the three Fe(III) complexes in methanol or buffered (pH approximately 2) 50:50 (v/v) methanol-water mixtures were determined using various spectroscopic methods: UV-vis absorption, X-ray absorption, extended X-ray absorption fine structure and electron paramagnetic resonance. All three systems showed both a 1:1 and 2:1 ligand-Fe(III) stoichiometry, but presented different coordination properties. Conditional formation constants (pH approximately 2) were determined for both the 1:1 and 2:1 complexes in all three systems. Computation of the coordination-conformational energies by semiempirical methods indicated that the coordination in the case of the 2:1 complexes of pyochelin-Fe(III) and 3''-nor-NH-pyochelin-Fe(III) was asymmetrical, with one molecule of pyochelin (or 3''-nor-NH-pyochelin) tetradentately coordinated (O1, N1, N2 and O3) to the Fe(III), and the second molecule bound bidentately (O1, N1 or N2, O3), to complete the octahedral geometry. In contrast, two molecules of the methyl hydroxamate each provided a set of tridentate ligand atoms in the formation of the 2:1 ligand-Fe(III) complex. These results are consistent with the role of pyochelin in the uptake of iron by the FptA receptor in the outer membrane of Pseudomonas aeruginosa and in several gram-negative bacteria.
    No preview · Article · Jul 2006 · JBIC Journal of Biological Inorganic Chemistry
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    ABSTRACT: Using an improved synthesis of pyochelin, a siderophore common to several pathogenic Pseudomonas species, three functionalized pyochelin analogs I [R = Me3SiCH2CH2O2CNH, Me3SiCH2CH2O2CNHCH2C.tplbond.C, Me3SiCH2CH2O2CNH(CH2)3] were efficiently synthesized starting from appropriate 2-hydroxybenzonitriles II. [on SciFinder (R)]
    No preview · Article · Mar 2006 · Tetrahedron
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    ABSTRACT: Under iron limitation, Pseudomonas aeruginosa ATCC 15692 secretes a major siderophore, pyoverdine I (PvdI). This molecule chelates iron in the extracellular medium and shuttles it into the cells via a specific outer membrane transporter, FpvAI. PvdI consists of a fluorescent chromophore derived from 2,3-diamino-6,7-dihydroxyquinoline and containing one of the bidentate groups involved in iron chelation, linked to a peptide moiety containing the two other bidentate groups required for binding to Fe(3+). Kinetic studies, based on the fluorescence properties of this siderophore, showed that pH 8.0 was optimal for the binding of PvdI and PvdI-Fe to FpvAI. We investigated the mechanism of interaction of PvdI and PvdI-Fe with FpvAI, by synthesizing various analogues of this siderophore, determining their affinity for FpvAI in vitro and in vivo and their ability to transport iron, and interpreting the results obtained in light of the structure of FpvAI-PvdI. Our findings demonstrate that the succinyl moiety linked to the chromophore of PvdI and the first amino acid of the peptide moiety can be sterically hindered with no effect on binding or the iron uptake properties of PvdI-Fe. Moreover, the sequence and the structure of the peptide moiety of PvdI seems to be more important for the iron uptake step than for the binding of the siderophore to FpvAI. Finally, the efficiency of iron uptake and of recycling of the various PvdI analogues after iron release suggests that iron dissociates from PvdI on FpvAI or in the periplasm. All these data have serious implications for the specificity and mechanism of PvdI-mediated iron transport in P. aeruginosa.
    No preview · Article · Dec 2005 · Biochemistry
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    ABSTRACT: Under iron-deficient conditions, the Gram-negative bacterium Pseudomonas aeruginosa ATCC 15692 secretes a peptidic siderophore, pyoverdin PaA, composed of an aromatic chromophore derived from 2,3-diamino-6,7-dihydroxyquinoline and a partially cyclized octapeptide, D-Ser–L-Arg–D-Ser–L-FoOHOrn–(L-Lys–L-FoOHOrn–L-Thr–L-Thr) (FoOHOrn: δN-formyl-δN-hydroxyornithine), in which the C-terminal carboxyl group forms a peptidic bond with the primary amine of the L-Lys side chain. Ferric iron is chelated by the catechol group on the chromophore and the two hydroxyornithine side chains. In aqueous solution, the 1H-NMR spectrum of pyoverdin PaA–Ga(III), in which Ga(III) is used instead of Fe(III) for spectroscopic purposes, showed clear evidence of exchange broadening, preventing further structural characterization. The use of cryo-solvents allowed measurements to be made at temperatures as low as 253 K where two distinct conformations with roughly equivalent populations could be observed. 13C and 15N labeling of pyoverdin PaA enabled complete assignment of both forms of pyoverdin PaA–Ga(III) at 253 and 267 K, using triple-resonance multidimensional NMR experiments commonly applied to doubly labeled proteins. © 2005 Wiley Periodicals, Inc. Biopolymers 79: 139–149, 2005 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at
    Full-text · Article · Oct 2005 · Biopolymers
  • Gaëtan L. Mislin · Alain Burger · Mohamed A. Abdallah
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    ABSTRACT: Three pyochelin analogues and their methyl esters all containing a thiazole ring have been synthesised from the same Weinreb amide key intermediate. One of these analogues called HPTT-COOH, a molecule released in the course of pyochelin and yersiniabactin biosynthesis, was efficiently synthesised using a new base induced conversion of the key compound 2′-(2-hydroxyphenyl)- 2′-thiazoline-4′-(N-methoxy,N-methyl) carboxamide into 2′-(2-hydroxyphenyl)-2′-thiazole-4′-(N-methoxy,N-methyl) carboxamide. Graphical Abstract
    No preview · Article · Apr 2005 · ChemInform
  • Cédric Klumpp · Alain Burger · Gaëtan L Mislin · Mohamed A Abdallah
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    ABSTRACT: A novel and straightforward total synthesis of cepabactin and its iron (III) complex is described. The latter compound was compared and identified to that obtained from the cultures of Burkholderia cepacia. On treatment of the growth medium of two different strains of B. cepacia with ferric chloride, we have isolated and characterized an unexpected mixed complex of iron (III), cepabactin and pyochelin.
    No preview · Article · Apr 2005 · Bioorganic & Medicinal Chemistry Letters
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    ABSTRACT: The pyoverdine outer membrane receptor FpvA from Pseudomonas aeruginosa translocates ferric-pyoverdine across the outer membrane via an energy consuming mechanism that involves the inner membrane energy transducing complex of TonB-ExbB-ExbD and the proton motive force. We solved the crystal structure of FpvA loaded with iron-free pyoverdine at 3.6 angstroms resolution. The pyoverdine receptor is folded in two domains: a transmembrane 22-stranded beta-barrel domain occluded by an N-terminal domain containing a mixed four-stranded beta-sheet (the plug). The beta-strands of the barrel are connected by long extracellular loops and short periplasmic turns. The iron-free pyoverdine is bound at the surface of the receptor in a pocket lined with aromatic residues while the extracellular loops do not completely cover the pyoverdine binding site. The TonB box, which is involved in intermolecular contacts with the TonB protein of the inner membrane, is observed in an extended conformation. Comparison of this first reported structure of an iron-siderophore transporter from a bacterium other than Escherichia coli with the known structures of the E.coli TonB-dependent transporters reveals a high structural homology and suggests that a common sensing mechanism exists for the iron-loading status in all bacterial iron siderophore transporters.
    No preview · Article · Apr 2005 · Journal of Molecular Biology
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    ABSTRACT: FpvA, the pyoverdine outer-membrane receptor from Pseudomonas aeruginosa, is involved in iron uptake when bacteria grow under iron limitation. Crystals of the in vivo pyoverdine-loaded FpvA were obtained under several crystallization conditions using different detergents. A native data set was collected at 3.6 A resolution and a three-wavelength MAD data set was collected at 3.6 A resolution using crystals of selenomethionine-substituted protein. The crystals grew under similar conditions and both belong to space group C2, but have different unit-cell parameters.
    No preview · Article · Sep 2004 · Acta Crystallographica Section D Biological Crystallography

  • No preview · Article · Aug 2004 · Acta Crystallographica Section A Foundations of Crystallography
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    ABSTRACT: Azotobacter vinelandii, a nitrogen-fixing soil bacterium, secretes in iron deficiency azotobactin delta, a highly fluorescent pyoverdin-like chromopeptidic hexadentate siderophore. The chromophore, derived from 2,3-diamino-6,7 dihydroxyquinoline, is bound to a peptide chain of 10 amino acids: (L)-Asp-(D)-Ser-(L)-Hse-Gly-(D)-beta-threo-HOAsp-(L)-Ser-(D)-Cit-(L)-Hse-(L)-Hse lactone-(D)-N(delta)-Acetyl, N(delta)-HOOrn. Azotobactin delta has three different iron(III) binding sites which are one hydroxamate group at the C-terminal end of the peptidic chain (N(delta)-Acetyl, N(delta)-HOOrn), one alpha-hydroxycarboxylic function in the middle of the chain (beta-threo-hydroxyaspartic acid), and one catechol group on the chromophore. The coordination properties of its iron(III) and iron(II) complexes were measured by spectrophotometry, potentiometry, and voltammetry after the determination of the acid-base functions of the uncomplexed free siderophore. Strongly negatively charged ferric species were observed at neutral p[H]'s corresponding to a predominant absolute configuration Lambda of the ferric complex in solution as deduced from CD measurements. The presence of an alpha-hydroxycarboxylic chelating group does not decrease the stability of the iron(III) complex when compared to the main trishydroxamate siderophores or to pyoverdins. The value of the redox potential of ferric azotobactin is highly consistent with a reductive step by physiological reductants for the iron release. Formation and dissociation kinetics of the azotobactin delta ferric complex point out that both ends of this long siderophore chain get coordinated to Fe(III) before the middle. The most striking result provided by fluorescence measurements is the lasting quenching of the fluorophore in the course of the protonation of the ferric azotobactin delta complex. Despite the release of the hydroxyacid and of the catechol, the fluorescence remains indeed quenched, when iron(III) is bound only to the hydroxamic acid, suggesting a folded conformation at this stage, around the metal ion, in contrast to the unfolded species observed for other siderophores such as ferrioxamine or pyoverdin PaA.
    No preview · Article · Mar 2004 · Inorganic Chemistry
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    A Zamri · I J Schalk · F Pattus · MA Abdallah
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    ABSTRACT: The synthesis and biological activities of four pyochelin analogues substituted in different parts of the molecule are reported: 5-NHBoc-pyochelin, 3"N-Boc-pyochelin, 3"-nor-NH-pyochelin and neopyochelin II, the enantiomer of natural pyochelin. All these compounds complex iron(III) and transport it at different rates into the cells of Pseudomonas aeruginosa.
    Full-text · Article · Jul 2003 · Bioorganic & Medicinal Chemistry Letters
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    ABSTRACT: Fur mutants (Mn(r)) of Pseudomonas aeruginosa Fe10 (FF13 and FF28) and PAO1 (FPA12) were evaluated for the pattern of deregulation of pyoverdin synthesis in iron-replete medium with Casamino acids [CAM(Fe)] or succinate [SM(Fe)]. With respect to siderophore synthesis, we found in CAM(Fe) medium two Fur phenotypes: FurA (full deregulation, FF13) and FurB (partial deregulation, FF28 and FPA12). Fur mutants compared to parental strains grew with slower specific growth rates on SM(0) and CAM(0) media in a stirred bioreactor. Fur mutants grew in SM(0) with mu about half of that in CAM(0).
    No preview · Article · Mar 2003 · Biotechnology Letters
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    ABSTRACT: In iron limitation conditions, Pseudomonas aeruginosa secretes a major fluorescent siderophore named pyoverdin (PaA). PaA has an extremely high affinity for Fe(3+) but also chelates other ions such as Al(3+) and Ga(3+) with a lower affinity. The transfer of PaA-Fe(3+) across the outer membrane of the bacteria is mediated by the receptor FpvA, a TonB-dependent outer membrane transport protein. FpvA binds the iron-free and iron-loaded forms of pyoverdin with similar affinities, but only PaA-Fe(3+) is taken up by the cell, suggesting that FpvA adopts different conformations depending on its loading status. We used time-resolved fluorescence spectroscopy to characterize the different forms of FpvA-PaA in vitro. We showed that the FpvA-PaA complex adopts two different conformations depending on how it was prepared (formed in vitro or in vivo prior to purification). The dihydroquinoline moiety of both conformers is fully protonated, or coordinated by protein charged groups, but the polarity of its environment, its solvent accessibility, and its rotational dynamics are much slower when the FpvA-PaA complex is formed in vivo than in vitro. In the presence of Ga(3+) or Al(3+) ions, the solvent accessibility and mobility of the dihydroquinoline moiety in the two FpvA-PaA complexes are intermediate between those observed for the metal-free ones. In addition, the Förster resonance energy transfer kinetics from FpvA tryptophan residues to the PaA chromophore differs from one complex to the other, revealing differences in one or more of the donor-acceptor topologies.
    No preview · Article · Jan 2003 · Biochemistry
  • Emeric Wasielewski · R Andrew Atkinson · Mohamed A Abdallah · Bruno Kieffer
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    ABSTRACT: In iron-deficient conditions, Azomonas macrocytogenes ATCC 12334 excretes a fluorescent siderophore called azoverdin, which is composed of a six-amino-acid peptide chain linked to a chromophore. Azoverdin chelates iron(III) very strongly, solubilizing it and transporting it back into the cells using an outer-membrane receptor. This compound is related to the pyoverdins, the peptidic siderophores of Pseudomonas, but differs in the site on the chromophore at which the peptide is covalently linked. This feature identifies azoverdin as a member of a new class of pyoverdins: the isopyoverdins. We report the three-dimensional structure of azoverdin-Ga(III) in solution. The use of orientational constraints obtained from the measurement of residual dipolar couplings using samples dissolved in a liquid crystalline medium allowed us to define the absolute configuration of the metal complex, which is Delta. The structure is characterized by a U-shape adopted by the peptide chain, with the N(delta)-acetyl-N(delta)-hydroxyornithine side chains adopting extended conformations in order to chelate the gallium ion. This conformation leaves a large open space permitting access to the gallium ion. The structural consequences of the particular isopyoverdin chemical structure are discussed in the context of the three-dimensional structures of other pyoverdins.
    No preview · Article · Nov 2002 · Biochemistry

Publication Stats

2k Citations
160.78 Total Impact Points


  • 1996-2008
    • University of Strasbourg
      • Faculté de chimie
      Strasburg, Alsace, France
  • 1990-2006
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 1988
    • Imperial College London
      Londinium, England, United Kingdom