The Experts below are selected from a list of 291 Experts worldwide ranked by ideXlab platform
Pierre Escoubas - One of the best experts on this subject based on the ideXlab platform.
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The Biochemical Toxin Arsenal from Ant Venoms
Toxins, 2016Co-Authors: Axel Touchard, Pierre Escoubas, Samira Aili, Eduardo Gonçalves Paterson Fox, Jérôme Orivel, Graham Nicholson, Alain DejeanAbstract:Ants (Formicidae) represent a taxonomically diverse group of hymenopterans with over 13,000 extant species, the majority of which inject or spray secretions from a venom gland. The evolutionary success of ants is mostly due to their unique eusociality that has permitted them to develop complex collaborative strategies, partly involving their venom secretions, to defend their nest against predators, microbial pathogens, ant competitors, and to hunt prey. Activities of ant venom include paralytic, cytolytic, haemolytic, allergenic, pro-inflammatory, insecticidal, antimicrobial, and pain-producing pharmacologic activities, while non-toxic functions include roles in chemical communication involving trail and sex pheromones, deterrents, and aggregators. While these diverse activities in ant venoms have until now been largely understudied due to the small venom yield from ants, modern analytical and venomic techniques are beginning to reveal the diversity of Toxin Structure and function. As such, ant venoms are distinct from other venomous animals, not only rich in linear, dimeric and disulfide-bonded peptides and bioactive proteins, but also other volatile and non-volatile compounds such as alkaloids and hydrocarbons. The present review details the unique Structures and pharmacologies of known ant venom proteinaceous and alkaloidal Toxins and their potential as a source of novel bioinsecticides and therapeutic agents.
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Structure and pharmacology of spider venom neuroToxins
Biochimie, 2000Co-Authors: Pierre Escoubas, Sylvie Diochot, Gerardo CorzoAbstract:Abstract Spider venoms are complex mixtures of neurotoxic peptides, proteins and low molecular mass organic molecules. Their neurotoxic activity is due to the interaction of the venom components with cellular receptors, in particular ion channels. Spider venoms have proven to be a rich source of highly specific peptide ligands for selected subtypes of potassium, sodium and calcium channels, and these Toxins have been used to elucidate the Structure and physiological roles of the channels in excitable and non-excitable cells. Spider peptides show great variability in their pharmacological activity and primary Structure but relative homogeneity in their secondary Structure. Following diverse molecular evolution mechanisms, and in particular selective hypermutation, short spider peptides appear to have functionally diversified while retaining a conserved molecular scaffold. This paper reviews the composition and pharmacology of spider venoms with emphasis on polypeptide Toxin Structure, mode of action and molecular evolution.
Dominique Housset - One of the best experts on this subject based on the ideXlab platform.
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Towards the charge-density study of proteins: a room-temperature scorpion-Toxin Structure at 0.96 Å resolution as a first test case.
Acta Crystallographica Section D Biological Crystallography, 2000Co-Authors: Dominique Housset, Juan C. Fontecilla-camps, Farid Benabicha, Virginie Pichon-pesme, Christian Jelsch, Andreas Maierhofer, Sylvain David, Claude LecomteAbstract:The number of protein Structures refined at a resolution higher than 1.0 A is continuously increasing. Subatomic Structures may deserve a more sophisticated model than the spherical atomic electron density. In very high resolution structural studies (d < 0.5 A) of small peptides, a multipolar atom model is used to describe the valence electron density. This allows a much more accurate determination of the anisotropic thermal displacement parameters and the estimate of atomic charges. This information is of paramount importance in the understanding of biological processes involving enzymes and metalloproteins. The Structure of the scorpion Androctonus australis Hector Toxin II has been refined at 0.96 A resolution using synchrotron diffraction data collected at room temperature. Refinement with a multipolar electron-density model in which the multipole populations are transferred from previous peptide studies led to the observation of valence electrons on covalent bonds of the most ordered residues. The refined net charges of the peptide-bond atoms were of the correct sign but were underestimated. Such protein-Structure refinements against higher resolution data collected at cryogenic temperature will enable the calculation of experimental atomic charges and properties such as electrostatic potentials.
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Towards the charge-density study of proteins: a room-temperature scorpion-Toxin Structure at 0.96 Å resolution as a first test case
Acta Crystallographica Section D: Biological Crystallography, 2000Co-Authors: Dominique Housset, Juan C. Fontecilla-camps, Farid Benabicha, Virginie Pichon-pesme, Christian Jelsch, Andreas Maierhofer, Sylvain David, Claude LecomteAbstract:The number of protein Structures refined at a resolution higher than 1.0 Å is continuously increasing. Subatomic Structures may deserve a more sophisticated model than the spherical atomic electron density. In very high resolution structural studies (d < 0.5 Å) of small peptides, a multipolar atom model is used to describe the valence electron density. This allows a much more accurate determination of the anisotropic thermal displacement parameters and the estimate of atomic charges. This information is of paramount importance in the understanding of biological processes involving enzymes and metalloproteins. The Structure of the scorpion $Androctonus australis$ Hector Toxin II has been refined at 0.96 Å resolution using synchrotron diffraction data collected at room temperature. Refinement with a multipolar electron-density model in which the multipole populations are transferred from previous peptide studies led to the observation of valence electrons on covalent bonds of the most ordered residues. The refined net charges of the peptide-bond atoms were of the correct sign but were underestimated. Such protein-Structure refinements against higher resolution data collected at cryogenic temperature will enable the calculation of experimental atomic charges and properties such as electrostatic potentials.
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Crystal Structure of Toxin II from the scorpion Androctonus australis Hector refined at 1.3 A resolution.
Journal of molecular biology, 1994Co-Authors: Dominique Housset, Catherine Habersetzer-rochat, Jean-pierre Astier, Juan C. Fontecilla-campsAbstract:Abstract The crystal Structure of Toxin II from the scorpion Androctonus australis Hector has been refined at 1·3 A resolution using restrained least-squares methods. The final R-factor is 0·148 for the 13,619 reflections between 7·0 A and 1·3 A resolution with F>2·5σ(F) and the bond length standard deviation from ideality is 0·017 A. Although minor changes have been introduced relative to the model previously refined at 1·8 A resolution, the use of higher-resolution data has allowed the modelling of some discrete disorder. Thus, three residues (including disulphide bridge) have been built with multiple conformations. Occupancies were refined for the 106 solvent molecules included in the model, nine of them with explicit multiple sites. There is well-defined electron density for some of the protein hydrogen atoms in the final difference Fourier map. A detailed description of the Toxin Structure is presented, along with a comparison with the high-resolution Structure of the related variant-3 scorpion Toxin
Claude Lecomte - One of the best experts on this subject based on the ideXlab platform.
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Towards the charge-density study of proteins: a room-temperature scorpion-Toxin Structure at 0.96 Å resolution as a first test case.
Acta Crystallographica Section D Biological Crystallography, 2000Co-Authors: Dominique Housset, Juan C. Fontecilla-camps, Farid Benabicha, Virginie Pichon-pesme, Christian Jelsch, Andreas Maierhofer, Sylvain David, Claude LecomteAbstract:The number of protein Structures refined at a resolution higher than 1.0 A is continuously increasing. Subatomic Structures may deserve a more sophisticated model than the spherical atomic electron density. In very high resolution structural studies (d < 0.5 A) of small peptides, a multipolar atom model is used to describe the valence electron density. This allows a much more accurate determination of the anisotropic thermal displacement parameters and the estimate of atomic charges. This information is of paramount importance in the understanding of biological processes involving enzymes and metalloproteins. The Structure of the scorpion Androctonus australis Hector Toxin II has been refined at 0.96 A resolution using synchrotron diffraction data collected at room temperature. Refinement with a multipolar electron-density model in which the multipole populations are transferred from previous peptide studies led to the observation of valence electrons on covalent bonds of the most ordered residues. The refined net charges of the peptide-bond atoms were of the correct sign but were underestimated. Such protein-Structure refinements against higher resolution data collected at cryogenic temperature will enable the calculation of experimental atomic charges and properties such as electrostatic potentials.
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Towards the charge-density study of proteins: a room-temperature scorpion-Toxin Structure at 0.96 Å resolution as a first test case
Acta Crystallographica Section D: Biological Crystallography, 2000Co-Authors: Dominique Housset, Juan C. Fontecilla-camps, Farid Benabicha, Virginie Pichon-pesme, Christian Jelsch, Andreas Maierhofer, Sylvain David, Claude LecomteAbstract:The number of protein Structures refined at a resolution higher than 1.0 Å is continuously increasing. Subatomic Structures may deserve a more sophisticated model than the spherical atomic electron density. In very high resolution structural studies (d < 0.5 Å) of small peptides, a multipolar atom model is used to describe the valence electron density. This allows a much more accurate determination of the anisotropic thermal displacement parameters and the estimate of atomic charges. This information is of paramount importance in the understanding of biological processes involving enzymes and metalloproteins. The Structure of the scorpion $Androctonus australis$ Hector Toxin II has been refined at 0.96 Å resolution using synchrotron diffraction data collected at room temperature. Refinement with a multipolar electron-density model in which the multipole populations are transferred from previous peptide studies led to the observation of valence electrons on covalent bonds of the most ordered residues. The refined net charges of the peptide-bond atoms were of the correct sign but were underestimated. Such protein-Structure refinements against higher resolution data collected at cryogenic temperature will enable the calculation of experimental atomic charges and properties such as electrostatic potentials.
Juan C. Fontecilla-camps - One of the best experts on this subject based on the ideXlab platform.
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Towards the charge-density study of proteins: a room-temperature scorpion-Toxin Structure at 0.96 Å resolution as a first test case.
Acta Crystallographica Section D Biological Crystallography, 2000Co-Authors: Dominique Housset, Juan C. Fontecilla-camps, Farid Benabicha, Virginie Pichon-pesme, Christian Jelsch, Andreas Maierhofer, Sylvain David, Claude LecomteAbstract:The number of protein Structures refined at a resolution higher than 1.0 A is continuously increasing. Subatomic Structures may deserve a more sophisticated model than the spherical atomic electron density. In very high resolution structural studies (d < 0.5 A) of small peptides, a multipolar atom model is used to describe the valence electron density. This allows a much more accurate determination of the anisotropic thermal displacement parameters and the estimate of atomic charges. This information is of paramount importance in the understanding of biological processes involving enzymes and metalloproteins. The Structure of the scorpion Androctonus australis Hector Toxin II has been refined at 0.96 A resolution using synchrotron diffraction data collected at room temperature. Refinement with a multipolar electron-density model in which the multipole populations are transferred from previous peptide studies led to the observation of valence electrons on covalent bonds of the most ordered residues. The refined net charges of the peptide-bond atoms were of the correct sign but were underestimated. Such protein-Structure refinements against higher resolution data collected at cryogenic temperature will enable the calculation of experimental atomic charges and properties such as electrostatic potentials.
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Towards the charge-density study of proteins: a room-temperature scorpion-Toxin Structure at 0.96 Å resolution as a first test case
Acta Crystallographica Section D: Biological Crystallography, 2000Co-Authors: Dominique Housset, Juan C. Fontecilla-camps, Farid Benabicha, Virginie Pichon-pesme, Christian Jelsch, Andreas Maierhofer, Sylvain David, Claude LecomteAbstract:The number of protein Structures refined at a resolution higher than 1.0 Å is continuously increasing. Subatomic Structures may deserve a more sophisticated model than the spherical atomic electron density. In very high resolution structural studies (d < 0.5 Å) of small peptides, a multipolar atom model is used to describe the valence electron density. This allows a much more accurate determination of the anisotropic thermal displacement parameters and the estimate of atomic charges. This information is of paramount importance in the understanding of biological processes involving enzymes and metalloproteins. The Structure of the scorpion $Androctonus australis$ Hector Toxin II has been refined at 0.96 Å resolution using synchrotron diffraction data collected at room temperature. Refinement with a multipolar electron-density model in which the multipole populations are transferred from previous peptide studies led to the observation of valence electrons on covalent bonds of the most ordered residues. The refined net charges of the peptide-bond atoms were of the correct sign but were underestimated. Such protein-Structure refinements against higher resolution data collected at cryogenic temperature will enable the calculation of experimental atomic charges and properties such as electrostatic potentials.
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Crystal Structure of Toxin II from the scorpion Androctonus australis Hector refined at 1.3 A resolution.
Journal of molecular biology, 1994Co-Authors: Dominique Housset, Catherine Habersetzer-rochat, Jean-pierre Astier, Juan C. Fontecilla-campsAbstract:Abstract The crystal Structure of Toxin II from the scorpion Androctonus australis Hector has been refined at 1·3 A resolution using restrained least-squares methods. The final R-factor is 0·148 for the 13,619 reflections between 7·0 A and 1·3 A resolution with F>2·5σ(F) and the bond length standard deviation from ideality is 0·017 A. Although minor changes have been introduced relative to the model previously refined at 1·8 A resolution, the use of higher-resolution data has allowed the modelling of some discrete disorder. Thus, three residues (including disulphide bridge) have been built with multiple conformations. Occupancies were refined for the 106 solvent molecules included in the model, nine of them with explicit multiple sites. There is well-defined electron density for some of the protein hydrogen atoms in the final difference Fourier map. A detailed description of the Toxin Structure is presented, along with a comparison with the high-resolution Structure of the related variant-3 scorpion Toxin
Isabel Gomez - One of the best experts on this subject based on the ideXlab platform.
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role of alkaline phosphatase from manduca sexta in the mechanism of action of bacillus thuringiensis cry1ab Toxin
Journal of Biological Chemistry, 2010Co-Authors: Ivan Arenas, Alejandra Bravo, Mario Soberon, Isabel GomezAbstract:Cry Toxins produced by Bacillus thuringiensis have been recognized as pore-forming Toxins whose primary action is to lyse midgut epithelial cells in their target insect. In the case of the Cry1A Toxins, a prepore oligomeric intermediate is formed after interaction with cadherin receptor. The Cry1A oligomer then interacts with glycosylphosphatidylinositol-anchored receptors. Two Manduca sexta glycosylphosphatidylinositol-anchored proteins, aminopeptidase (APN) and alkaline phosphatase (ALP), have been shown to bind Cry1Ab, although their role in toxicity remains to be determined. Detection of Cry1Ab binding proteins by ligand blot assay revealed that ALP is preferentially expressed earlier during insect development, because it was found in the first larval instars, whereas APN is induced later after the third larval instar. The binding of Cry1Ab oligomer to pure preparations of APN and ALP showed that this Toxin Structure interacts with both receptors with high affinity (apparent K(d) = 0.6 nM), whereas the monomer showed weaker binding (apparent K(d) = 101.6 and 267.3 nM for APN and ALP, respectively). Several Cry1Ab nontoxic mutants located in the exposed loop 2 of domain II or in beta-16 of domain III were affected in binding to APN and ALP, depending on their oligomeric state. In particular monomers of the nontoxic domain III, the L511A mutant did not bind ALP but retained APN binding, suggesting that initial interaction with ALP is critical for toxicity. Our data suggest that APN and ALP fulfill two roles. First APN and ALP are initial receptors promoting the localization of Toxin monomers in the midgut microvilli before interaction with cadherin. Then APN and ALP function as secondary receptors mediating oligomer insertion into the membrane. However, the expression pattern of these receptors and the phenotype of L511A mutant suggest that ALP may have a predominant role in Toxin action because Cry Toxins are highly effective against the neonate larvae that is the target for pest control programs.
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role of alkaline phosphatase from manduca sexta in the mechanism of action of bacillus thuringiensis cry1ab Toxin
Journal of Biological Chemistry, 2010Co-Authors: Ivan Arenas, Alejandra Bravo, Mario Soberon, Isabel GomezAbstract:Cry Toxins produced by Bacillus thuringiensis have been recognized as pore-forming Toxins whose primary action is to lyse midgut epithelial cells in their target insect. In the case of the Cry1A Toxins, a prepore oligomeric intermediate is formed after interaction with cadherin receptor. The Cry1A oligomer then interacts with glycosylphosphatidylinositol-anchored receptors. Two Manduca sexta glycosylphosphatidylinositol-anchored proteins, aminopeptidase (APN) and alkaline phosphatase (ALP), have been shown to bind Cry1Ab, although their role in toxicity remains to be determined. Detection of Cry1Ab binding proteins by ligand blot assay revealed that ALP is preferentially expressed earlier during insect development, because it was found in the first larval instars, whereas APN is induced later after the third larval instar. The binding of Cry1Ab oligomer to pure preparations of APN and ALP showed that this Toxin Structure interacts with both receptors with high affinity (apparent Kd = 0.6 nm), whereas the monomer showed weaker binding (apparent Kd = 101.6 and 267.3 nm for APN and ALP, respectively). Several Cry1Ab nontoxic mutants located in the exposed loop 2 of domain II or in β-16 of domain III were affected in binding to APN and ALP, depending on their oligomeric state. In particular monomers of the nontoxic domain III, the L511A mutant did not bind ALP but retained APN binding, suggesting that initial interaction with ALP is critical for toxicity. Our data suggest that APN and ALP fulfill two roles. First APN and ALP are initial receptors promoting the localization of Toxin monomers in the midgut microvilli before interaction with cadherin. Then APN and ALP function as secondary receptors mediating oligomer insertion into the membrane. However, the expression pattern of these receptors and the phenotype of L511A mutant suggest that ALP may have a predominant role in Toxin action because Cry Toxins are highly effective against the neonate larvae that is the target for pest control programs.
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structural changes of the cry1ac oligomeric pre pore from bacillus thuringiensis induced by n acetylgalactosamine facilitates Toxin membrane insertion
Biochemistry, 2006Co-Authors: Liliana Pardolopez, Isabel Gomez, Carolina Rausell, Jorge Sanchez, Mario Soberon, Alejandra BravoAbstract:The primary action of Cry Toxins produced by Bacillus thuringiensisis to lyse midgut epithelial cells in their target insect by forming lytic pores. The Toxin -receptor interaction is a complex process, involving multiple interactions with different receptor and carbohydrate molecules. It has been proposed that Cry1A Toxins sequentially interact with a cadherin receptor, leading to the formation of a pre-pore oligomer Structure, and that the oligomeric Structure binds to glycosylphosphatidyl-inositol-anchored aminopeptidase-N (APN) receptor. The Cry1Ac Toxin specifically recognizes the N-acetylgalactosamine (GalNAc) carbohydrate present in the APN receptor from Manduca sexta larvae. In this work, we show that the Cry1Ac pre-pore oligomer has a higher binding affinity with APN than the monomeric Toxin. The effects of GalNAc binding on the Toxin Structure were studied in the monomeric Cry1Ac, in the soluble pre-pore oligomeric Structure, and in its membrane inserted state by recording the fluorescence status of the tryptophan (W) residues. Our results indicate that the W residues of Cry1Ac have a different exposure to the solvent when compared with that of the closely related Cry1Ab Toxin. GalNAc binding specifically affects the exposure of W545 in the pre-pore oligomer in contrast to the monomer where GalNAc binding did not affect the fluorescence of the Toxin. These results indicate a subtle conformational change in the GalNAc binding pocket in the pre-pore oligomer that could explain the increased binding affinity of the Cry1Ac pre-pore to APN. Although our analysis did not reveal major structural changes in the pore-forming domain I upon GalNAc binding, it showed that sugar interaction enhanced membrane insertion of soluble pre-pore oligomeric Structure. Therefore, the data presented here permits to propose a model in which the interaction of Cry1Ac pre-pore oligomer with APN receptor facilitates membrane insertion and pore formation.