Pseudonajatoxin b, or Pt-b, is a highly potent and lethal long-chain α-neurotoxin found in the venom of the eastern brown snake (''

Pseudonaja textilis The eastern brown snake (''Pseudonaja textilis''), often referred to as the common brown snake, is a species of extremely venomous snake in the Family (biology), family Elapidae. The species is native to eastern and central Australia and souther ...

''). While the

pharmacodynamics Pharmacodynamics (PD) is the study of the biochemistry, biochemical and physiology, physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or comb ...

of pseudonajatoxin b are currently undocumented, α-neurotoxins are known to cause neuromuscular

paralysis Paralysis (: paralyses; also known as plegia) is a loss of Motor skill, motor function in one or more Skeletal muscle, muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory d ...

by blocking cholinergic neurotransmission.

Source

Pseudonajatoxin b is present in the venom of the highly lethal eastern brown snake, ''

'', which is the leading cause of snakebites in Australia. The concentration of pseudonajatoxin b in venom of South Australian specimens is up to a hundred times higher than in those from Queensland. 

Chemistry

Structure and homology

Pseudonajatoxin b is composed of a single polypeptide chain of 71 amino acids and features five disulphide bridges. It exhibits 61-73% sequence homology with other long neurotoxins. Distinctive characteristics of pseudonajatoxin b include a high occurrence of

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the p ...

residues, particularly at positions 49 and 54, where

valine Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deproton ...

s are usually present. Moreover, it contains an additional amino acid in the loop between Cys-46 and Cys-58.

Protein family

Alphafold_structure_model_of_pseudonajatoxin_b

Pseudonajatoxin b is a type of

three-finger toxin Three-finger toxins (abbreviated 3FTx) are a protein superfamily of small toxin proteins found in the venom of snakes. Three-finger toxins are in turn members of a larger superfamily of three-finger protein domains which includes non-toxic prote ...

, which are characterized by a structure of three loops that emerge from a

hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...

core. Specifically, it falls within the long-chain subfamily of the α-neurotoxin group.

Target and mechanism of action

Although the

of pseudonajatoxin b have not been documented, α-neurotoxins generally exhibit some common traits. Long-chain α-neurotoxins have been shown to bind with high affinity to both muscular and neuronal

nicotinic acetylcholine receptors Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...

. These receptors serve as the primary mediator of muscle contraction in response to nerve impulses. Additionally, they are present in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

, where they play an important role in autonomic processes, including the regulation of heart rate and respiration. By acting as competitive

antagonists An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain. This disruption in

neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron ...

effectively leads to neuromuscular paralysis. Importantly, since the activation of nicotinic acetylcholine receptors requires the binding of two acetylcholine molecules, the blockage of just one binding site by an α-neurotoxin is sufficient to prevent channel opening. Furthermore, long-chain α-neurotoxins typically bind tightly and irreversibly to nicotinic receptors, resulting in permanent channel inactivation once they are bound.

Toxicity and treatment

Pseudonajatoxin b is a highly potent toxin, with a

median lethal dose In toxicology, the median lethal dose, LD50 (abbreviation for " lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a given substance. The value of LD50 for a substance is the dose re ...

(LD₅₀) of 15 pg/kg in mice. Although the specific lethal mechanisms of pseudonajatoxin b remain unknown, it is well established that both α-neurotoxins and the venom of ''P. textilis'' induce paralysis, leading to death through

asphyxiation Asphyxia or asphyxiation is a condition of deficient supply of oxygen to the body which arises from abnormal breathing. Asphyxia causes generalized hypoxia, which affects all the tissues and organs, some more rapidly than others. There are ...

. Currently, no treatment specific for pseudonajatoxin b has been documented. However, envenomation from ''Pseudonaja textilis'' can be treated with

snake antivenom Snake antivenom is a medication made up of antibodies used to treat snake bites by venomous snakes. It is a type of antivenom. It is a biological product that typically consists of venom neutralizing antibodies derived from a host animal, s ...

made from

antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...

, specifically horse immuno-globulins. Despite this, studies have shown that brown snake antivenom has low efficacy against ''Pseudonaja textilis'' venom.

References

{{DEFAULTSORT:Pseudonajatoxin b Snake toxins Peptides Neurotoxins