Solution spatial structure of apamin as derived from NMR study

Bystrov, V. F.; Okhanov, V. V.; Мирошников, А. И.; Ovchinnikov, Yu.A.

doi:10.1016/0014-5793(80)81010-6

Cited by 49 publications

(45 citation statements)

References 13 publications

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“…The solution structure of apamin, a powerful neurotoxin isolated from honeybee venom,1 is well established 2–7. It is characterized by the cystine‐stabilized α‐helix motif (CSH),8–10 where the half‐cystine residues in positions 11 and 15 are part of a short α‐helix and cross‐linked via two disulfide bridges to the half‐cysteines 1 and 3, respectively, which are located at the N‐terminus of the peptide chain itself folded in a β‐turn to produce the globular structure.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and conformational analysis of apamin analogues with natural and non-natural cystine/selenocystine connectivities

et al. 2000

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Section: Introductionmentioning

confidence: 99%

Synthesis and conformational analysis of apamin analogues with natural and non-natural cystine/selenocystine connectivities

et al. 2000

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“…For this purpose, a wide variety of physical/chemical methods are employed. For example, the three-dimensional arrangement of critical side chain groups and backbone conformations can be analyzed via NMR spectroscopy [44,45], X-ray crystallography [46], circular dichroism measurements [47], and computational methods [48]. The next step is to find a suitable non-peptide scaffold which can impart the same 3D topographic structural features as the peptide based on conformational analysis, computational chemistry and 3D modeling.…”

Section: General Considerations For the Design Of Hmc3r Selective Agomentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Ligands Selective for the Melanocortin-3 Receptor

Hruby¹,

Cai²,

Cain³

et al. 2007

curr top med chem

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The processed products of the proopiomelanocortin gene (ACTH, α-MSH, β-MSH, γ-MSH, etc.) interact with five melanocortin receptors, the MC1R, MC2R, MC3R, MC4R, and MC5R to modulate and control many important biological functions crucial for good health both peripherally (as hormones) and centrally (as neurotransmitters). Pivotal biological functions include pigmentation, adrenal function, response to stress, fear/flight, energy homeostasis, feeding behavior, sexual function and motivation, pain, immune response, and many others, and are believed to be involved in many disease states including pigmentary disorders, adrenal disorders, obesity, anorexia, prolonged and neuropathic pain, inflammatory response, etc. The roeianocortin-3 receptor (MC3R) is found primarily in the brain and spinal cord and also in the periphery, and its biological functions are still not well understood. Here we review some of the biological functions attributed to the MC3R, and then examine in more detail efforts to design and synthesize ligands that are potent and selective for the MC3R, which might help resolve the many questions still remaining about its function. Though some progress has been made, there is still much to be done in this critical area.

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“…The disulfide bridges were determined as described by Callewaert et al (1968). The CD spectra of apamin(1-15) and Acm,-apamin were recorded at the CEN Saclay, Gif sur Yvette, France.…”

Section: Deprotection Of the Cysteine Residues Refolding Of Peptidesmentioning

confidence: 99%

“…Apamin is a basic peptide with 18 amino acid residues (Haux et al, 1967;Shipolini et al, 1967) and two disulfide bridges (Callewaert et al, 1968;Fig. 1).…”

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Binding and toxicity of apamin

Labbé-Jullié

Granier

Alberício

et al. 1991

European Journal of Biochemistry

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The structural features of apamin, a natural octadecapeptide from bee venom, enabling binding to its receptor and the expression of toxicity in mice, have been delineated by studying the effects on binding and toxicity of chemical modifications and amino acid substitutions in synthetic analogues. The results obtained indicate that the only hydrophobic residue, leucine at position 10, can be changed to alanine without a significant decrease in the specific activity. The need for a correct conformation has been established and also the importance of Gln-17 and the side chains of Arg-13 and Arg-14 (besides the charge effects). The interaction of apamin with its receptor, a calcium-activated potassium channel, is thus mediated by a precise topology around these three residues. Due to the ability to detect very low specific activities for some of the analogues, it has been shown that, individually, none of these interactions constitute an essential criteria for binding per se, but that their presence is necessary for the high specific activity of the toxin.Of all the components characterized in the venom of the bee (Apis mellifera mellifera), the peptide apamin is the most toxic to mammals (Habermann and Reiz, 1965). Apamin passes the blood/brain barrier where its site of action is the central nervous system (Habermann and Cheng-Raude, 1975). Banks et al. (1979) discovered recently that apamin acts as a specific blocker of a calcium-dependent potassium channel in guinea-pig taenia coli and in liver, implying that apamin receptors are also located in the periphery.Receptor characterization was first made possible by the availability of a pure '251-labelled derivative of apamin (Hugues et al., 1982a) and later by the availability of two wellcharacterized photosensitive probes of '251-labelled apamin (Seagar et al., 1985(Seagar et al., , 1986. Studies on various tissues revealed a unique receptor in the rat central nervous system (Seagar et al., 1986), guinea-pig smooth muscle, liver and rat heart (Marqu2ze et al., 1987), which was composed of several protein subunits.Apamin is a basic peptide with 18 amino acid residues (Haux et al., 1967;Shipolini et al., 1967) and two disulfide bridges (Callewaert et al., 1968; Fig. 1). Solid-phase synthesis of apamin has been performed (Van Rietschoten et al., 1975) which permits structure/activity studies to be carried out, based on chemical modification of the natural peptide and which are complemented by studies on synthetic analogues. The activities were compared by determining the median lethal Abbreviations. Acm4-apamin, tetraacetamidomethyl apamin; (cHxO2]apamin, apamin modified on its two arginine residues by cyclohexanedione; LDS0, median lethal dose; apamin(x-y), synthetic analogue of apamin composed of amino acid residues x-y. dose (LD50) after subcutaneous injection in mice and for some, by binding experiments performed on rat brain membranes. In summary, the following observations were made. (a) Chemical modification of the natural peptide at the two free amino groups o...

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Solution spatial structure of apamin as derived from NMR study

Cited by 49 publications

References 13 publications

Synthesis and conformational analysis of apamin analogues with natural and non-natural cystine/selenocystine connectivities

Synthesis and conformational analysis of apamin analogues with natural and non-natural cystine/selenocystine connectivities

Design, Synthesis and Biological Evaluation of Ligands Selective for the Melanocortin-3 Receptor

Binding and toxicity of apamin

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