Browse
Submit Data
Databases
API
Help

Dataset Information

8 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cross Pharmacological, Biochemical and Computational Studies of a Human Kv3.1b Inhibitor from Androctonus australis Venom.

ABSTRACT: The voltage-gated K⁺ channels Kv3.1 display fast activation and deactivation kinetics and are known to have a crucial contribution to the fast-spiking phenotype of certain neurons. AahG50, as a natural product extracted from Androctonus australis hector venom, inhibits selectively Kv3.1 channels. In the present study, we focused on the biochemical and pharmacological characterization of the component in AahG50 scorpion venom that potently and selectively blocks the Kv3.1 channels. We used a combined optimization through advanced biochemical purification and patch-clamp screening steps to characterize the peptide in AahG50 active on Kv3.1 channels. We described the inhibitory effect of a toxin on Kv3.1 unitary current in black lipid bilayers. In silico, docking experiments are used to study the molecular details of the binding. We identified the first scorpion venom peptide inhibiting Kv3.1 current at 170 nM. This toxin is the alpha-KTx 15.1, which occludes the Kv3.1 channel pore by means of the lysine 27 lateral chain. This study highlights, for the first time, the modulation of the Kv3.1 by alpha-KTx 15.1, which could be an interesting starting compound for developing therapeutic biomolecules against Kv3.1-associated diseases.

SUBMITTER: Maatoug S

PROVIDER: S-EPMC8618407 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Diabody mixture providing full protection against experimental scorpion envenoming with crude Androctonus australis venom.

Project description:Androctonus australis is primarily involved in envenomations in North Africa, notably in Tunisia and Algeria, and constitutes a significant public health problem in this region. The toxicity of the venom is mainly due to various neurotoxins that belong to two distinct structural and immunological groups, group I (the AahI and AahIII toxins) and group II (AahII). Here, we report the use of a diabody mixture in which the molar ratio matches the characteristics of toxins and polymorphism of the venom. The mixture consists of the Db9C2 diabody (anti-group I) and the Db4C1op diabody (anti-AahII), the latter being modified to facilitate in vitro production and purification. The effectiveness of the antivenom was tested in vivo under conditions simulating scorpion envenomation. The intraperitoneal injection of 30 ?g of the diabody mixture protected almost all the mice exposed to 3 LD(50) s.c. of venom. We also show that the presence of both diabodies is necessary for the animals to survive. Our results are the first demonstration of the strong protective power of small quantities of antivenom used in the context of severe envenomation with crude venom.

| S-EPMC3340170 | biostudies-literature

Androctonus australis

Project description:Androctonus australis overview

| PRJNA355929 | ENA

Androctonus australis

Project description:Androctonus australis Transcriptome or Gene expression

| PRJNA268459 | ENA

Androctonus australis

Project description:Androctonus australis Transcriptome or Gene expression

| PRJNA270676 | ENA

AaTs-1: A Tetrapeptide from Androctonus australis Scorpion Venom, Inhibiting U87 Glioblastoma Cells Proliferation by p53 and FPRL-1 Up-Regulations.

Project description:Glioblastoma is an aggressive cancer, against which medical professionals are still quite helpless, due to its resistance to current treatments. Scorpion toxins have been proposed as a promising alternative for the development of effective targeted glioblastoma therapy and diagnostic. However, the exploitation of the long peptides could present disadvantages. In this work, we identified and synthetized AaTs-1, the first tetrapeptide from Androctonus australis scorpion venom (Aa), which exhibited an antiproliferative effect specifically against human glioblastoma cells. Both the native and synthetic AaTs-1 were endowed with the same inhibiting effect on the proliferation of U87 cells with an IC50 of 0.56 mM. Interestingly, AaTs-1 was about two times more active than the anti-glioblastoma conventional chemotherapeutic drug, temozolomide (TMZ), and enhanced its efficacy on U87 cells. AaTs-1 showed a significant similarity with the synthetic peptide WKYMVm, an agonist of a G-coupled formyl-peptide receptor, FPRL-1, known to be involved in the proliferation of glioma cells. Interestingly, the tetrapeptide triggered the dephosphorylation of ERK, p38, and JNK kinases. It also enhanced the expression of p53 and FPRL-1, likely leading to the inhibition of the store operated calcium entry. Overall, our work uncovered AaTs-1 as a first natural potential FPRL-1 antagonist, which could be proposed as a promising target to develop new generation of innovative molecules used alone or in combination with TMZ to improve glioblastoma treatment response. Its chemical synthesis in non-limiting quantity represents a valuable advantage to design and develop low-cost active analogues to treat glioblastoma cancer.

| S-EPMC8704564 | biostudies-literature

Computational Studies of Snake Venom Toxins.

Project description:Most snake venom toxins are proteins, and participate to envenomation through a diverse array of bioactivities, such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic or neurotoxic effects. The venom of a single snake species contains hundreds of toxins, and the venoms of the 725 species of venomous snakes represent a large pool of potentially bioactive proteins. Despite considerable discovery efforts, most of the snake venom toxins are still uncharacterized. Modern bioinformatics tools have been recently developed to mine snake venoms, helping focus experimental research on the most potentially interesting toxins. Some computational techniques predict toxin molecular targets, and the binding mode to these targets. This review gives an overview of current knowledge on the ~2200 sequences, and more than 400 three-dimensional structures of snake toxins deposited in public repositories, as well as of molecular modeling studies of the interaction between these toxins and their molecular targets. We also describe how modern bioinformatics have been used to study the snake venom protein phospholipase A2, the small basic myotoxin Crotamine, and the three-finger peptide Mambalgin.

| S-EPMC5793095 | biostudies-literature

Computational Studies of Venom Peptides Targeting Potassium Channels.

Project description:Small peptides isolated from the venom of animals are potential scaffolds for ion channel drug discovery. This review article mainly focuses on the computational studies that have advanced our understanding of how various toxins interfere with the function of K? channels. We introduce the computational tools available for the study of toxin-channel interactions. We then discuss how these computational tools have been fruitfully applied to elucidate the mechanisms of action of a wide range of venom peptides from scorpions, spiders, and sea anemone.

| S-EPMC4690127 | biostudies-literature

Serotherapy against Voltage-Gated Sodium Channel-Targeting αToxins from Androctonus Scorpion Venom.

Project description:Because of their venom lethality towards mammals, scorpions of the Androctonus genus are considered a critical threat to human health in North Africa. Several decades of exploration have led to a comprehensive inventory of their venom components at chemical, pharmacological, and immunological levels. Typically, these venoms contain selective and high affinity ligands for the voltage-gated sodium (Nav) and potassium (Kv) channels that dictate cellular excitability. In the well-studied Androctonusaustralis and Androctonusmauretanicus venoms, almost all the lethality in mammals is due to the so-called α-toxins. These peptides commonly delay the fast inactivation process of Nav channels, which leads to increased sodium entry and a subsequent cell membrane depolarization. Markedly, their neutralization by specific antisera has been shown to completely inhibit the venom's lethal activity, because they are not only the most abundant venom peptide but also the most fatal. However, the structural and antigenic polymorphisms in the α-toxin family pose challenges to the design of efficient serotherapies. In this review, we discuss past and present accomplishments to improve serotherapy against Androctonus scorpion stings.

| S-EPMC6410273 | biostudies-literature

Biochemical and Proteomic Characterization, and Pharmacological Insights of Indian Red Scorpion Venom Toxins.

Project description:The Indian red scorpion (Mesobuthus tamulus) is one of the world's deadliest scorpions, with stings representing a life-threatening medical emergency. This species is distributed throughout the Indian sub-continent, including eastern Pakistan, eastern Nepal, and Sri Lanka. In India, Indian red scorpions are broadly distributed in western Maharashtra, Saurashtra, Kerala, Andhra Pradesh, Tamil Nadu, and Karnataka; however, fatal envenomations have been recorded primarily in the Konkan region of Maharashtra. The Indian red scorpion venom proteome comprises 110 proteins belonging to 13 venom protein families. The significant pharmacological activity is predominantly caused by the low molecular mass non-enzymatic Na+ and K+ ion channel toxins. Other minor toxins comprise 15.6% of the total venom proteome. Indian red scorpion stings induce the release of catecholamine, which leads to pathophysiological abnormalities in the victim. A strong correlation has been observed between venom proteome composition and local (swelling, redness, heat, and regional lymph node involvement) and systemic (tachycardia, mydriasis, hyperglycemia, hypertension, toxic myocarditis, cardiac failure, and pulmonary edema) manifestations. Immediate administration of antivenom is the preferred treatment for Indian red scorpion stings. However, scorpion-specific antivenoms have exhibited poor immunorecognition and neutralization of the low molecular mass toxins. The proteomic analysis also suggests that Indian red scorpion venom is a rich source of pharmacologically active molecules that may be envisaged as drug prototypes. The following review summarizes the progress made towards understanding the venom proteome of the Indian red scorpion and addresses the current understanding of the pathophysiology associated with its sting.

| S-EPMC8505525 | biostudies-literature

Systematic and computational identification of Androctonus crassicauda long non-coding RNAs.

Project description:The potential function of long non-coding RNAs in regulating neighbor protein-coding genes has attracted scientists' attention. Despite the important role of lncRNAs in biological processes, a limited number of studies focus on non-model animal lncRNAs. In this study, we used a stringent step-by-step filtering pipeline and machine learning-based tools to identify the specific Androctonus crassicauda lncRNAs and analyze the features of predicted scorpion lncRNAs. 13,401 lncRNAs were detected using pipeline in A. crassicauda transcriptome. The blast results indicated that the majority of these lncRNAs sequences (12,642) have no identifiable orthologs even in closely related species and those considered as novel lncRNAs. Compared to lncRNA prediction tools indicated that our pipeline is a helpful approach to distinguish protein-coding and non-coding transcripts from RNA sequencing data of species without reference genomes. Moreover, analyzing lncRNA characteristics in A. crassicauda uncovered that lower protein-coding potential, lower GC content, shorter transcript length, and less number of isoform per gene are outstanding features of A. crassicauda lncRNAs transcripts.

| S-EPMC7907363 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data