The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Dominique Marion - One of the best experts on this subject based on the ideXlab platform.
-
a structural homologue of colipase in Black Mamba venom revealed by nmr floating disulphide bridge analysis
Journal of Molecular Biology, 1998Co-Authors: Jerome Boisbouvier, Jean-pierre Albrand, Martin Blackledge, Hugues Schweitz, Michel Lazdunski, Michel Jaquinod, Dominique MarionAbstract:The solution structure of Mamba intestinal toxin 1 (MIT1), isolated from Dendroaspis polylepis polylepis venom, has been determined. This molecule is a cysteine-rich polypeptide exhibiting no recognised family membership. Resistance to MIT1 to classical specific endoproteases produced contradictory NMR and biochemical information concerning disulphide-bridge topology. We have used distance restraints allowing ambiguous partners between S atoms in combination with NMR-derived structural information, to correctly determine the disulphide-bridge topology. The resultant solution structure of MIT1, determined to a resolution of 0.5 A, reveals an unexpectedly similar global fold with respect to colipase, a protein involved in fatty acid digestion. Colipase exhibits an analogous resistance to endoprotease activity, indicating for the first time the possible topological origins of this biochemical property. The biochemical and structural homology permitted us to propose a mechanically related digestive function for MIT1 and provides novel information concerning snake venom protein evolution.
-
NMR and restrained molecular dynamics study of the three-dimensional solution structure of toxin FS2, a specific blocker of the L-type calcium channel, isolated from Black Mamba venom.
Biochemistry, 1995Co-Authors: Jean-pierre Albrand, Martin Blackledge, Franck Pascaud, Michelle Hollecker, Dominique MarionAbstract:The three-dimensional solution structure of toxin FS2, a 60-residue polypeptide isolated from the venom of Black Mamba snake (Dendroaspis polylepis polylepis), has been determined by nuclear magnetic resonance spectroscopy. Using 600 NOE constraints and 55 dihedral angle constraints, a set of 20 structures obtained from distance-geometry calculations was further refined by molecular dynamics calculations using a combined simulated annealing-restrained MD protocol. The resulting 20 conformers, taken to represent the solution structure, give an average rmsd of 1.2 A for their backbone atoms, relative to the average structure. The overall resulting three-fingered structure is similar to those already observed in several postsynaptic neurotoxins, cardiotoxins, and fasciculins, which all share with toxin FS2 the same network of four disulfide bridges. The overall concavity of the molecule, considered as a flat bottomed dish, is oriented toward the C-terminal loop of the molecule. This orientation is similar to that of fasciculins and cardiotoxins but opposite to that of neurotoxins. On the basis of the local rms displacements between the 20 conformers, the structure of the first loop appears to be less well defined in FS2 than in the previously reported neurotoxin structures, but fasciculin 1 shows a similar trend with particularly high temperature factors for this part of the X-ray structure. The concave side which presents most of the positively charged residues is quite similar in FS2 and fasciculin 1. The main difference is shown by the convex side of the third loop, mostly hydrophobic in FS2, in contrast to the pair of negatively charged aspartates in fasciculin 1. This difference could be one of the factors leading to the distinct pharmacological properties-L-type calcium channel blocker for FS2 and cholinesterase inhibitor for fasciculin--observed for these two subgroups of the "angusticeps-type" toxins.
-
Proteinase inhibitor homologues as potassium channel blockers
Nature Structural Biology, 1994Co-Authors: Jean-marc Lancelin, Michelle Hollecker, Marie-françoise Foray, Marc Poncin, Dominique MarionAbstract:We report here the NMR structure of dendrotoxin I, a powerful potassium channel blocker from the venom of the African Elapidae snake Dendroaspis polylepis polylepis (Black Mamba), calculated from an experimentally–derived set of 719 geometric restraints. The backbone of the toxin superimposes on bovine pancreatic trypsin inhibitor (BPTI) with a root–mean–square deviation of
-
Proteinase inhibitor homologues as potassium channel blockers.
Nature structural biology, 1994Co-Authors: Jean-marc Lancelin, Michelle Hollecker, Marie-françoise Foray, Marc Poncin, Dominique MarionAbstract:We report here the NMR structure of dendrotoxin I, a powerful potassium channel blocker from the venom of the African Elapidae snake Dendroaspis polylepis polylepis (Black Mamba), calculated from an experimentally–derived set of 719 geometric restraints. The backbone of the toxin superimposes on bovine pancreatic trypsin inhibitor (BPTI) with a root–mean–square deviation of
-
sequence specific 1h nmr assignment and secondary structure of Black Mamba dendrotoxin i a highly selective blocker of voltage gated potassium channels
FEBS Journal, 1993Co-Authors: Marie-françoise Foray, Michelle Hollecker, Jean-marc Lancelin, Dominique MarionAbstract:The secondary structure of dendrotoxin I, an important constituent of the venom of the African Black Mamba snake Dendroaspis polylepis polylepis, was determined in aqueous solution by two-dimensional methods. Complete sequence-specific 1H-NMR assignment was obtained with the exception of the backbone amide proton of Gly39 and Cys40. Dendrotoxin I is based on a central antiparallel β-sheet and two small helices located at the N- and the C-terminal extremities. These secondary-structural units occur at exactly the same places in the amino acid sequence as those of bovine pancreatic trypsin inhibitor (BPTI), with which dendrotoxin I shares 33% sequence similarity. According to the disulfide-bridge positions and the long-range NOE observed these secondary-structural elements fold in a similar manner to BPTI. This similarity allows an hypothesis according to which dendrotoxin I could derive from an ancestral Kunitz-type proteinase inhibitor. This ancestor would have been heavily mutated at amino acid positions not critical for gross structure. The spatial locations of the solvent-exposed amino acids concerned could therefore serve as a guideline for interpretation of the structure/activity relationship of dendrotoxin I for the blockage of voltage-sensitive potassium channels of which dendrotoxin I is a strong inhibitor. The possible connections with other polypeptide toxins that block related ion currents is discussed.
Sabine Scarzello - One of the best experts on this subject based on the ideXlab platform.
-
Black Mamba venom peptides target acid sensing ion channels to abolish pain
Nature, 2012Co-Authors: Sylvie Diochot, Anne Baron, Miguel Salinas, Dominique Douguet, Sabine ScarzelloAbstract:Polypeptide toxins have played a central part in understanding physiological and physiopathological functions of ion channels. In the field of pain, they led to important advances in basic research and even to clinical applications. Acid-sensing ion channels (ASICs) are generally considered principal players in the pain pathway, including in humans. A snake toxin activating peripheral ASICs in nociceptive neurons has been recently shown to evoke pain. Here we show that a new class of three-finger peptides from another snake, the Black Mamba, is able to abolish pain through inhibition of ASICs expressed either in central or peripheral neurons. These peptides, which we call Mambalgins, are not toxic in mice but show a potent analgesic effect upon central and peripheral injection that can be as strong as morphine. This effect is, however, resistant to naloxone, and Mambalgins cause much less tolerance than morphine and no respiratory distress. Pharmacological inhibition by Mambalgins combined with the use of knockdown and knockout animals indicates that blockade of heteromeric channels made of ASIC1a and ASIC2a subunits in central neurons and of ASIC1b-containing channels in nociceptors is involved in the analgesic effect of Mambalgins. These findings identify new potential therapeutic targets for pain and introduce natural peptides that block them to produce a potent analgesia.
Michel Lazdunski - One of the best experts on this subject based on the ideXlab platform.
-
mit1 a Black Mamba toxin with a new and highly potent activity on intestinal contraction
FEBS Letters, 1999Co-Authors: Hugues Schweitz, Sylvie Diochot, Pierre Pacaud, Danielle Moinier, Michel LazdunskiAbstract:Mamba intestinal toxin (MIT(1)) isolated from Dendroaspis polylepis venom is a 81 amino acid polypeptide cross-linked by five disulphide bridges. MIT(1) has a very potent action on guinea-pig intestinal contractility. MIT(1) (1 nM) potently contracts longitudinal ileal muscle and distal colon, and this contraction is equivalent to that of 40 mM K(+). Conversely MIT(1) relaxes proximal colon again as potently as 40 mM K(+). The MIT(1)-induced effects are antagonised by tetrodotoxin (1 microM) in proximal and distal colon but not in longitudinal ileum. The MIT(1)-induced relaxation of the proximal colon is reversibly inhibited by the NO synthase inhibitor L-NAME (200 microM). (125)I-labelled MIT(1) binds with a very high affinity to both ileum and brain membranes (K(d)=1.3 pM and 0.9 pM, and B(max)=30 fmol/mg and 26 fmol/mg, respectively). MIT(1) is a very highly selective toxin for a receptor present both in the CNS and in the smooth muscle and which might be an as yet unidentified K(+) channel.
-
a structural homologue of colipase in Black Mamba venom revealed by nmr floating disulphide bridge analysis
Journal of Molecular Biology, 1998Co-Authors: Jerome Boisbouvier, Jean-pierre Albrand, Martin Blackledge, Hugues Schweitz, Michel Lazdunski, Michel Jaquinod, Dominique MarionAbstract:The solution structure of Mamba intestinal toxin 1 (MIT1), isolated from Dendroaspis polylepis polylepis venom, has been determined. This molecule is a cysteine-rich polypeptide exhibiting no recognised family membership. Resistance to MIT1 to classical specific endoproteases produced contradictory NMR and biochemical information concerning disulphide-bridge topology. We have used distance restraints allowing ambiguous partners between S atoms in combination with NMR-derived structural information, to correctly determine the disulphide-bridge topology. The resultant solution structure of MIT1, determined to a resolution of 0.5 A, reveals an unexpectedly similar global fold with respect to colipase, a protein involved in fatty acid digestion. Colipase exhibits an analogous resistance to endoprotease activity, indicating for the first time the possible topological origins of this biochemical property. The biochemical and structural homology permitted us to propose a mechanically related digestive function for MIT1 and provides novel information concerning snake venom protein evolution.
-
Calciseptine, a peptide isolated from Black Mamba venom, is a specific blocker of the L-type calcium channel.
Proceedings of the National Academy of Sciences of the United States of America, 1991Co-Authors: J R De Weille, Hugues Schweitz, P Maes, André Tartar, Michel LazdunskiAbstract:The venom of the Black Mamba contains a 60-amino acid peptide called calciseptine. The peptide has been fully sequenced. It is a smooth muscle relaxant and an inhibitor of cardiac contractions. Its physiological action resembles that of drugs, such as the 1,4-dihydropyridines, which are important in the treatment of cardiovascular diseases. Calciseptine, like the 1,4-dihydropyridines, selectively blocks L-type Ca2+ channels and is totally inactive on other voltage-dependent Ca2+ channels such as N-type and T-type channels. To our knowledge, it is the only natural polypeptide that has been shown to be a specific inhibitor of L-type Ca2+ channels.
Michelle Hollecker - One of the best experts on this subject based on the ideXlab platform.
-
NMR and restrained molecular dynamics study of the three-dimensional solution structure of toxin FS2, a specific blocker of the L-type calcium channel, isolated from Black Mamba venom.
Biochemistry, 1995Co-Authors: Jean-pierre Albrand, Martin Blackledge, Franck Pascaud, Michelle Hollecker, Dominique MarionAbstract:The three-dimensional solution structure of toxin FS2, a 60-residue polypeptide isolated from the venom of Black Mamba snake (Dendroaspis polylepis polylepis), has been determined by nuclear magnetic resonance spectroscopy. Using 600 NOE constraints and 55 dihedral angle constraints, a set of 20 structures obtained from distance-geometry calculations was further refined by molecular dynamics calculations using a combined simulated annealing-restrained MD protocol. The resulting 20 conformers, taken to represent the solution structure, give an average rmsd of 1.2 A for their backbone atoms, relative to the average structure. The overall resulting three-fingered structure is similar to those already observed in several postsynaptic neurotoxins, cardiotoxins, and fasciculins, which all share with toxin FS2 the same network of four disulfide bridges. The overall concavity of the molecule, considered as a flat bottomed dish, is oriented toward the C-terminal loop of the molecule. This orientation is similar to that of fasciculins and cardiotoxins but opposite to that of neurotoxins. On the basis of the local rms displacements between the 20 conformers, the structure of the first loop appears to be less well defined in FS2 than in the previously reported neurotoxin structures, but fasciculin 1 shows a similar trend with particularly high temperature factors for this part of the X-ray structure. The concave side which presents most of the positively charged residues is quite similar in FS2 and fasciculin 1. The main difference is shown by the convex side of the third loop, mostly hydrophobic in FS2, in contrast to the pair of negatively charged aspartates in fasciculin 1. This difference could be one of the factors leading to the distinct pharmacological properties-L-type calcium channel blocker for FS2 and cholinesterase inhibitor for fasciculin--observed for these two subgroups of the "angusticeps-type" toxins.
-
Proteinase inhibitor homologues as potassium channel blockers
Nature Structural Biology, 1994Co-Authors: Jean-marc Lancelin, Michelle Hollecker, Marie-françoise Foray, Marc Poncin, Dominique MarionAbstract:We report here the NMR structure of dendrotoxin I, a powerful potassium channel blocker from the venom of the African Elapidae snake Dendroaspis polylepis polylepis (Black Mamba), calculated from an experimentally–derived set of 719 geometric restraints. The backbone of the toxin superimposes on bovine pancreatic trypsin inhibitor (BPTI) with a root–mean–square deviation of
-
Proteinase inhibitor homologues as potassium channel blockers.
Nature structural biology, 1994Co-Authors: Jean-marc Lancelin, Michelle Hollecker, Marie-françoise Foray, Marc Poncin, Dominique MarionAbstract:We report here the NMR structure of dendrotoxin I, a powerful potassium channel blocker from the venom of the African Elapidae snake Dendroaspis polylepis polylepis (Black Mamba), calculated from an experimentally–derived set of 719 geometric restraints. The backbone of the toxin superimposes on bovine pancreatic trypsin inhibitor (BPTI) with a root–mean–square deviation of
-
sequence specific 1h nmr assignment and secondary structure of Black Mamba dendrotoxin i a highly selective blocker of voltage gated potassium channels
FEBS Journal, 1993Co-Authors: Marie-françoise Foray, Michelle Hollecker, Jean-marc Lancelin, Dominique MarionAbstract:The secondary structure of dendrotoxin I, an important constituent of the venom of the African Black Mamba snake Dendroaspis polylepis polylepis, was determined in aqueous solution by two-dimensional methods. Complete sequence-specific 1H-NMR assignment was obtained with the exception of the backbone amide proton of Gly39 and Cys40. Dendrotoxin I is based on a central antiparallel β-sheet and two small helices located at the N- and the C-terminal extremities. These secondary-structural units occur at exactly the same places in the amino acid sequence as those of bovine pancreatic trypsin inhibitor (BPTI), with which dendrotoxin I shares 33% sequence similarity. According to the disulfide-bridge positions and the long-range NOE observed these secondary-structural elements fold in a similar manner to BPTI. This similarity allows an hypothesis according to which dendrotoxin I could derive from an ancestral Kunitz-type proteinase inhibitor. This ancestor would have been heavily mutated at amino acid positions not critical for gross structure. The spatial locations of the solvent-exposed amino acids concerned could therefore serve as a guideline for interpretation of the structure/activity relationship of dendrotoxin I for the blockage of voltage-sensitive potassium channels of which dendrotoxin I is a strong inhibitor. The possible connections with other polypeptide toxins that block related ion currents is discussed.
-
Sequence‐specific 1H‐NMR assignment and secondary structure of Black Mamba dendrotoxin I, a highly selective blocker of voltage‐gated potassium channels
European journal of biochemistry, 1993Co-Authors: Marie-françoise Foray, Michelle Hollecker, Jean-marc Lancelin, Dominique MarionAbstract:The secondary structure of dendrotoxin I, an important constituent of the venom of the African Black Mamba snake Dendroaspis polylepis polylepis, was determined in aqueous solution by two-dimensional methods. Complete sequence-specific 1H-NMR assignment was obtained with the exception of the backbone amide proton of Gly39 and Cys40. Dendrotoxin I is based on a central antiparallel β-sheet and two small helices located at the N- and the C-terminal extremities. These secondary-structural units occur at exactly the same places in the amino acid sequence as those of bovine pancreatic trypsin inhibitor (BPTI), with which dendrotoxin I shares 33% sequence similarity. According to the disulfide-bridge positions and the long-range NOE observed these secondary-structural elements fold in a similar manner to BPTI. This similarity allows an hypothesis according to which dendrotoxin I could derive from an ancestral Kunitz-type proteinase inhibitor. This ancestor would have been heavily mutated at amino acid positions not critical for gross structure. The spatial locations of the solvent-exposed amino acids concerned could therefore serve as a guideline for interpretation of the structure/activity relationship of dendrotoxin I for the blockage of voltage-sensitive potassium channels of which dendrotoxin I is a strong inhibitor. The possible connections with other polypeptide toxins that block related ion currents is discussed.
Marie-françoise Foray - One of the best experts on this subject based on the ideXlab platform.
-
Proteinase inhibitor homologues as potassium channel blockers
Nature Structural Biology, 1994Co-Authors: Jean-marc Lancelin, Michelle Hollecker, Marie-françoise Foray, Marc Poncin, Dominique MarionAbstract:We report here the NMR structure of dendrotoxin I, a powerful potassium channel blocker from the venom of the African Elapidae snake Dendroaspis polylepis polylepis (Black Mamba), calculated from an experimentally–derived set of 719 geometric restraints. The backbone of the toxin superimposes on bovine pancreatic trypsin inhibitor (BPTI) with a root–mean–square deviation of
-
Proteinase inhibitor homologues as potassium channel blockers.
Nature structural biology, 1994Co-Authors: Jean-marc Lancelin, Michelle Hollecker, Marie-françoise Foray, Marc Poncin, Dominique MarionAbstract:We report here the NMR structure of dendrotoxin I, a powerful potassium channel blocker from the venom of the African Elapidae snake Dendroaspis polylepis polylepis (Black Mamba), calculated from an experimentally–derived set of 719 geometric restraints. The backbone of the toxin superimposes on bovine pancreatic trypsin inhibitor (BPTI) with a root–mean–square deviation of
-
sequence specific 1h nmr assignment and secondary structure of Black Mamba dendrotoxin i a highly selective blocker of voltage gated potassium channels
FEBS Journal, 1993Co-Authors: Marie-françoise Foray, Michelle Hollecker, Jean-marc Lancelin, Dominique MarionAbstract:The secondary structure of dendrotoxin I, an important constituent of the venom of the African Black Mamba snake Dendroaspis polylepis polylepis, was determined in aqueous solution by two-dimensional methods. Complete sequence-specific 1H-NMR assignment was obtained with the exception of the backbone amide proton of Gly39 and Cys40. Dendrotoxin I is based on a central antiparallel β-sheet and two small helices located at the N- and the C-terminal extremities. These secondary-structural units occur at exactly the same places in the amino acid sequence as those of bovine pancreatic trypsin inhibitor (BPTI), with which dendrotoxin I shares 33% sequence similarity. According to the disulfide-bridge positions and the long-range NOE observed these secondary-structural elements fold in a similar manner to BPTI. This similarity allows an hypothesis according to which dendrotoxin I could derive from an ancestral Kunitz-type proteinase inhibitor. This ancestor would have been heavily mutated at amino acid positions not critical for gross structure. The spatial locations of the solvent-exposed amino acids concerned could therefore serve as a guideline for interpretation of the structure/activity relationship of dendrotoxin I for the blockage of voltage-sensitive potassium channels of which dendrotoxin I is a strong inhibitor. The possible connections with other polypeptide toxins that block related ion currents is discussed.
-
Sequence‐specific 1H‐NMR assignment and secondary structure of Black Mamba dendrotoxin I, a highly selective blocker of voltage‐gated potassium channels
European journal of biochemistry, 1993Co-Authors: Marie-françoise Foray, Michelle Hollecker, Jean-marc Lancelin, Dominique MarionAbstract:The secondary structure of dendrotoxin I, an important constituent of the venom of the African Black Mamba snake Dendroaspis polylepis polylepis, was determined in aqueous solution by two-dimensional methods. Complete sequence-specific 1H-NMR assignment was obtained with the exception of the backbone amide proton of Gly39 and Cys40. Dendrotoxin I is based on a central antiparallel β-sheet and two small helices located at the N- and the C-terminal extremities. These secondary-structural units occur at exactly the same places in the amino acid sequence as those of bovine pancreatic trypsin inhibitor (BPTI), with which dendrotoxin I shares 33% sequence similarity. According to the disulfide-bridge positions and the long-range NOE observed these secondary-structural elements fold in a similar manner to BPTI. This similarity allows an hypothesis according to which dendrotoxin I could derive from an ancestral Kunitz-type proteinase inhibitor. This ancestor would have been heavily mutated at amino acid positions not critical for gross structure. The spatial locations of the solvent-exposed amino acids concerned could therefore serve as a guideline for interpretation of the structure/activity relationship of dendrotoxin I for the blockage of voltage-sensitive potassium channels of which dendrotoxin I is a strong inhibitor. The possible connections with other polypeptide toxins that block related ion currents is discussed.