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Dominique Marion - One of the best experts on this subject based on the ideXlab platform.
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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.
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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.
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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
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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
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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.
Kurt Wüthrich - One of the best experts on this subject based on the ideXlab platform.
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Nuclear Magnetic Resonance Solution Structure of Dendrotoxin K from the Venom of Dendroaspis polylepis polylepis
Journal of molecular biology, 1993Co-Authors: Kurt D. Berndt, Peter Güntert, Kurt WüthrichAbstract:Nuclear-Magnetic-Resonance Solution Structure of Dendrotoxin-K from the Venom of Dendroaspis-polylepis-polylepis
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The program ASNO for computer-supported collection of NOE upper distance constraints as input for protein structure determination
Journal of Biomolecular NMR, 1993Co-Authors: Peter Güntert, Kurt D. Berndt, Kurt WüthrichAbstract:A new program, ASNO (‘ AS sign NO es’), for computer-supported NOE cross-peak assignments is described. ASNO is used for structure refinement in several rounds of NOESY cross-peak assignments and 3D structure calculations, where the preliminary structures are used as a reference to resolve ambiguities in NOE assignments which are otherwise based on the chemical shifts available from the sequence-specific resonance assignments. The practical use of ASNO for proteins is illustrated with the structure determination of Dendrotoxin K from Dendroaspis polylepis polylepis .
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nuclear magnetic resonance solution structure of the α neurotoxin from the black mamba Dendroaspis polylepis polylepis
Journal of Molecular Biology, 1992Co-Authors: Larry R Brown, Kurt WüthrichAbstract:Abstract The three-dimensional structure in solution of the α-neurotoxin from the black mamba ( Dendroaspis polylepis polylepis ) has been determined by nuclear magnetic resonance spectroscopy. A high quality structure for this 60-residue protein was obtained from 656 NOE distance constraints and 143 dihedral angle constraints, using the distance geometry program DIANA for the structure calculation and AMBER for restrained energy minimization. For a group of 20 conformers used to represent the solution structure, the average root-mean-square deviation value calculated for the polypeptide backbone heavy atoms relative to the mean structure was 0.45 A. The protein consists of a core region from which three finger-like loops extend outwards. It includes a short, two-stranded antiparallel β-sheet of residues 1–5 and 13–17, a three-stranded antiparallel β-sheet involving residues 23–31, 34–42 and 51–55, and four disulfide bridges in the core region. There is also extensive non-regular hydrogen bonding between the carboxy-terminal tail of the polypeptide chain and the rest of the core region. Comparison with the crystal structure of erabutoxin-b indicates that the structure of α-neurotoxin is quite similar to other neurotoxin structures, but that local structural differences are seen in regions thought to be important for binding of neurotoxins to the acetylcholine receptor. For two regions of the α-neurotoxin structure there is evidence for an equilibrium between multiple conformations, which might be related to conformational rearrangements upon binding to the receptor. Overall, the α-neurotoxin presents itself as a protein with a stable core and flexible surface areas that interact with the acetylcholine receptor in such a way that high affinity binding is achieved by conformational rearrangements of the deformable regions of the neurotoxin structure.
Michelle Hollecker - One of the best experts on this subject based on the ideXlab platform.
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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.
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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
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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
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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.
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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.
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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
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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
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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.
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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.
Jean-marc Lancelin - One of the best experts on this subject based on the ideXlab platform.
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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
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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
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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.
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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.