Snake venom toxins the primary structure of protein S4C11

Carlsson, Fritz H.H.

doi:10.1016/0005-2795(75)90186-5

Cited by 38 publications

(8 citation statements)

References 13 publications

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“…Specific determinants for ␣-cobratoxin include Arg 36 and Phe 65 (19,22). Of these critical residues for the muscle ␣␤␥␦ receptor, Trp 25 , Arg 33 and Arg 36 (in ␣-cobratoxin) and Glu 38 and Gly 34 (in erabutoxin-a) are present at homologous positions in candoxin ( Figs. 2A and 6A).…”

Section: Discussionmentioning

confidence: 99%

“…However, unlike in the long chain ␣-and -neurotoxins, the fifth disulfide bridge in weak toxins is located in loop I (N-terminal loop) (24). Toxins belonging to this class were first isolated from Naja melanoleuca venom (25) and were also referred to as the melanoleuca type (26,27) or the miscellaneous type of toxins (28). They are typically characterized by a lower order of toxicity (LD 50 varying from ϳ5 to 80 mg/kg) as opposed to prototype ␣-neurotoxins (LD 50 varying from ϳ 0.04 to 0.3 mg/kg) (29).…”

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confidence: 99%

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Candoxin, a Novel Toxin from Bungarus candidus, Is a Reversible Antagonist of Muscle (αβγδ) but a Poorly Reversible Antagonist of Neuronal α7 Nicotinic Acetylcholine Receptors

Nirthanan¹,

Charpantier²,

Gopalakrishnakone³

et al. 2002

Journal of Biological Chemistry

104

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In contrast to most short and long chain curaremimetic neurotoxins that produce virtually irreversible neuromuscular blockade in isolated nerve-muscle preparations, candoxin, a novel three-finger toxin from the Malayan krait Bungarus candidus, produced postjunctional neuromuscular blockade that was readily and completely reversible. Nanomolar concentrations of candoxin (IC 50 ‫؍‬ ϳ10 nM) also blocked acetylcholineevoked currents in oocyte-expressed rat muscle (␣␤␥␦) nicotinic acetylcholine receptors in a reversible manner. In contrast, it produced a poorly reversible block (IC 50 ‫؍‬ ϳ50 nM) of rat neuronal ␣7 receptors, clearly showing diverse functional profiles for the two nicotinic receptor subsets. Interestingly, candoxin lacks the helix-like segment cyclized by the fifth disulfide bridge at the tip of the middle loop of long chain neurotoxins, reported to be critical for binding to ␣7 receptors. However, its solution NMR structure showed the presence of some functionally invariant residues involved in the interaction of both short and long chain neurotoxins to muscle (␣␤␥␦) and long chain neurotoxins to ␣7 receptors. Candoxin is therefore a novel toxin that shares a common scaffold with long chain ␣-neurotoxins but possibly utilizes additional functional determinants that assist in recognizing neuronal ␣7 receptors.Curaremimetic or ␣-neurotoxins from snake venoms are well known to bind with high affinity and selectivity and in most instances, almost irreversibly to Torpedo and muscle (␣␤␥␦) nicotinic acetylcholine receptors (nAChR), 1 thereby affecting synaptic neurotransmission and producing flaccid paralysis (1, 2). They belong to a family of proteins called "three-finger toxins," which adopt a flat, leaf-like shape formed by three adjacent loops that emerge from a small globular core, which is the location of the four conserved disulfide bridges (3-9). Other members of this family include -bungarotoxins, which recognize neuronal nicotinic receptors (10), muscarinic toxins with selectivity toward distinct types of muscarinic receptors (11), fasciculins that inhibit acetylcholinesterase (12), calciseptins that block the L-type calcium channels (13,14), cardiotoxins (cytotoxins) that exert their toxicity by forming pores in cell membranes (15), and dendroaspins, which are antagonists of various cell adhesion processes (16). Despite their common structural fold and comparable affinity for the Torpedo and muscle (␣␤␥␦) nAChRs, ␣-neurotoxins are classified as short chain neurotoxins (e.g. erabutoxin-b (Laticauda semifasciata)) that have 60 -62 residues and four conserved disulfide bonds and long chain neurotoxins (e.g. ␣-bungarotoxin (Bungarus multicinctus); ␣-cobratoxin (Naja kaouthia)) with 66 -75 residues and five disulfide bonds (3). The additional disulfide bridge in long chain ␣-neurotoxins, as well in the neuronal -bungarotoxin (B. multicinctus) is located in the middle loop (loop II) (3,8,9). This fifth bridge, which cyclizes a helix-like conformation at the tip of loop II, has been reported to be cru...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Candoxin, a Novel Toxin from Bungarus candidus, Is a Reversible Antagonist of Muscle (αβγδ) but a Poorly Reversible Antagonist of Neuronal α7 Nicotinic Acetylcholine Receptors

Nirthanan¹,

Charpantier²,

Gopalakrishnakone³

et al. 2002

Journal of Biological Chemistry

104

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“…The first representative of "weak toxins," characterized by low toxicity, was isolated from Naja melanoleuca snake venom and sequenced in 1975 (1). Toxins of this type were later referred to as melanoleuca (2) or miscellaneous-type (3) toxins.…”

mentioning

confidence: 99%

“…However, most other three-fingered toxins, including cardiotoxins, muscarinic toxins, acetylcholinesterase inhibitors, and the so-called short chain ␣-neurotoxins, contain four disulfide bridges. A fifth disulfide bridge is present in the long chain ␣-neurotoxins, such as ␣-bungarotoxin (␣Bgt) 1 from Bungarus multicinctus or ␣-cobratoxin from Naja kaouthia (CTX) and -bungarotoxin (Bgt), which together with short ␣-neurotoxins are potent antagonists of different classes of nicotinic acetylcholine receptors (AChRs) (for reviews see Refs. 6 -8).…”

mentioning

confidence: 99%

“Weak Toxin” from Naja kaouthia Is a Nontoxic Antagonist of α7 and Muscle-type Nicotinic Acetylcholine Receptors

Utkin

Kukhtina

Kryukova

et al. 2001

Journal of Biological Chemistry

111

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A novel "weak toxin" (WTX) from Naja kaouthia snake venom competes with [125 I]␣-bungarotoxin for binding to the membrane-bound Torpedo californica acetylcholine receptor (AChR), with an IC 50 of ϳ2.2 M. In this respect, it is ϳ300 times less potent than neurotoxin II from Naja oxiana and ␣-cobratoxin from N. kaouthia, representing short-type and long-type ␣-neurotoxins, respectively. WTX and ␣-cobratoxin displaced [125 I]␣-bungarotoxin from the Escherichia coli-expressed fusion protein containing the rat ␣7 AChR N-terminal domain 1-208 preceded by glutathione S-transferase with IC 50 values of 4.3 and 9.1 M, respectively, whereas for neurotoxin II the IC 50 value was >100 M. Micromolar concentrations of WTX inhibited acetylcholine-activated currents in Xenopus oocyte-expressed rat muscle AChR and human and rat ␣7 AChRs, inhibiting the latter most efficiently (IC 50 of ϳ8.3 M). Thus, a virtually nontoxic "three-fingered" protein WTX, although differing from ␣-neurotoxins by an additional disulfide in the N-terminal loop, can be classified as a weak ␣-neurotoxin. It differs from the short chain ␣-neurotoxins, which potently block the muscle-type but not the ␣7 AChRs, and is closer to the long ␣-neurotoxins, which have comparable potency against the above-mentioned AChR types.

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“…The positions of the four disulfide bonds were in agreement with those of neurotoxins and cardiotoxins, while the fifth, positioned in the first loop, differed from that of the long neurotoxins and K-neurotoxins situated in the second loop. This specific disulfide bond type was also discovered in miscellaneous type neurotoxins from Naja species (8,9). But BMNTL2 shared a rather low degree of identical residues with the miscellaneous type neurotoxins.…”

Section: Vol 46 No 4 1998mentioning

confidence: 58%

cDNA cloning and sequence analysis of six neurotoxin‐like proteins from Chinese continental banded krait

et al. 1998

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SUMMARY The cDNAs encoding six neurotoxin-like proteins were cloned from the total RNA isolated from one venom gland of Bungarus multicinctus multicinctus by reverse transcription-polymerase chain reaction. Although they shared a high degree of nucleotide sequence homology, the deduced proteins displayed a rather low extent of identical residues with the exception that the 21 residue signal peptides were highly conserved. Each mature protein consisted of 65, 66 or 68 amino acids with four or five disulfide bonds respectively. Comparative sequence analyses showed that they were structurally related to neurotoxin homologues. Phylogenetic analyses implied that they might represent two different evolutionary branches.

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Snake venom toxins the primary structure of protein S4C11

Cited by 38 publications

References 13 publications

Candoxin, a Novel Toxin from Bungarus candidus, Is a Reversible Antagonist of Muscle (αβγδ) but a Poorly Reversible Antagonist of Neuronal α7 Nicotinic Acetylcholine Receptors

Candoxin, a Novel Toxin from Bungarus candidus, Is a Reversible Antagonist of Muscle (αβγδ) but a Poorly Reversible Antagonist of Neuronal α7 Nicotinic Acetylcholine Receptors

“Weak Toxin” from Naja kaouthia Is a Nontoxic Antagonist of α7 and Muscle-type Nicotinic Acetylcholine Receptors

cDNA cloning and sequence analysis of six neurotoxin‐like proteins from Chinese continental banded krait

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