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https://www.readbyqxmd.com/read/29027927/conotoxins-as-tools-to-understand-the-physiological-function-of-voltage-gated-calcium-cav-channels
#1
REVIEW
David Ramírez, Wendy Gonzalez, Rafael A Fissore, Ingrid Carvacho
Voltage-gated calcium (CaV) channels are widely expressed and are essential for the completion of multiple physiological processes. Close regulation of their activity by specific inhibitors and agonists become fundamental to understand their role in cellular homeostasis as well as in human tissues and organs. CaV channels are divided into two groups depending on the membrane potential required to activate them: High-voltage activated (HVA, CaV1.1-1.4; CaV2.1-2.3) and Low-voltage activated (LVA, CaV3.1-3.3)...
October 13, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28986377/stenotrophomonas-like-bacteria-are-widespread-symbionts-in-cone-snail-venom-ducts
#2
Joshua P Torres, Ma Diarey Tianero, Jose Miguel D Robes, Jason C Kwan, Jason S Biggs, Gisela P Concepcion, Baldomero M Olivera, Margo G Haygood, Eric W Schmidt
Cone snails are biomedically important sources of peptide drugs, but it is not known whether snail-associated bacteria affect venom chemistry. To begin to answer this question, we performed 16S rRNA gene amplicon sequencing of eight cone snail species, comparing their microbiomes with each other and with those from a variety of other marine invertebrates. We show that the cone snail microbiome is distinct from those in other marine invertebrates and conserved in specimens from around the world, including the Philippines, Guam, California, and Florida...
October 6, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28943883/in-silico-analysis-of-binding-interaction-of-conantokins-with-nmda-receptors-for-potential-therapeutic-use-in-alzheimer-s-disease
#3
Maleeha Waqar, Sidra Batool
BACKGROUND: The N-methyl-D-aspartate (NMDA) receptors are glutamate receptors that play vital roles in central nervous system development and are involved in synaptic plasticity, which is an essential process for learning and memory. The subunit N-methyl D-aspartate receptor subtype 2B (NR2B) is the chief excitatory neurotransmitter receptor in the mammalian brain. Disturbances in the neurotransmission mediated by the NMDA receptor are caused by its overexposure to glutamate neurotransmitter and can be treated by its binding to an antagonist...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28922871/divergence-of-the-venom-exogene-repertoire-in-two-sister-species-of-turriconus
#4
Qing Li, Neda Barghi, Aiping Lu, Alexander E Fedosov, Pradip K Bandyopadhyay, Arturo O Lluisma, Gisela P Concepcion, Mark Yandell, Baldomero M Olivera, Helena Safavi-Hemami
The genus Conus comprises approximately 700 species of venomous marine cone snails that are highly efficient predators of worms, snails, and fish. In evolutionary terms, cone snails are relatively young with the earliest fossil records occurring in the Lower Eocene, 55 Ma. The rapid radiation of cone snail species has been accompanied by remarkably high rates of toxin diversification. To shed light on the molecular mechanisms that accompany speciation, we investigated the toxin repertoire of two sister species, Conus andremenezi and Conus praecellens, that were until recently considered a single variable species...
September 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28891599/expression-in-escherichia-coli-of-fusion-protein-comprising-%C3%AE-conotoxin-txib-and-preservation-of-selectivity-to-nicotinic-acetylcholine-receptors-in-the-purified-product
#5
Jinpeng Yu, Xiaopeng Zhu, Yang Yang, Sulan Luo, Dongting Zhangsun
Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels, which are widely distributed in the central and peripheral nervous system. The α6β2* nAChR is an important subtype, which is closely associated with nicotine addiction and movement disorders etc. α-conotoxin TxIB with 16-amino acid residues specifically targets α6β2* nAChR with no obvious effect on other nAChR subtypes. However, chemical synthesis of TxIB is expensive, and the quantity of native TxIB extracted from cone snail is limited...
September 11, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28856545/oxidative-folding-of-conopeptides-modified-by-conus-protein-disulfide-isomerase
#6
Lei Wang, Xiaomin Wang, Zhenghua Ren, Wei Tang, Qiong Zou, Jinxing Wang, Shangwu Chen, Han Zhang, Anlong Xu
Protein disulfide isomerase is a type of enzyme that catalyses the oxidation, isomerization and reduction of disulfide bonds. Conotoxins that containing disulfide bonds are likely substrates of protein disulfide isomerise. Here, we cloned 12 protein disulfide isomerise genes from 12 different cone snail species that inhabited the sea near Sanya in China. The full-length amino acid sequences of these protein disulfide isomerase genes share a high degree of homology, including the same -CGHC- active site sequence and -RDEL- endoplasmic reticulum retention signal...
August 30, 2017: Protein Journal
https://www.readbyqxmd.com/read/28718820/a-transcriptomic-survey-of-ion-channel-based-conotoxins-in-the-chinese-tubular-cone-snail-conus-betulinus
#7
Yu Huang, Chao Peng, Yunhai Yi, Bingmiao Gao, Qiong Shi
Conotoxins in the venom of cone snails (Conus spp.) are a mixture of active peptides that work as blockers, agonists, antagonists, or inactivators of various ion channels. Recently we reported a high-throughput method to identify 215 conotoxin transcripts from the Chinese tubular cone snail, C. betulinus. Here, based on the previous datasets of four transcriptomes from three venom ducts and one venom bulb, we explored ion channel-based conotoxins and predicted their related ion channel receptors. Homologous analysis was also performed for the most abundant ion channel protein, voltage-gated potassium (Kv; with Kv1...
July 18, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28689025/venom-derived-peptide-inhibitors-of-voltage-gated-potassium-channels
#8
REVIEW
Raymond S Norton, K George Chandy
Voltage-gated potassium channels play a key role in human physiology and pathology. Reflecting their importance, numerous channelopathies have been characterised that arise from mutations in these channels or from autoimmune attack on the channels. Voltage-gated potassium channels are also the target of a broad range of peptide toxins from venomous organisms, including sea anemones, scorpions, spiders, snakes and cone snails; many of these peptides bind to the channels with high potency and selectivity. In this review we describe the various classes of peptide toxins that block these channels and illustrate the broad range of three-dimensional structures that support channel blockade...
July 5, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28684723/screening-and-validation-of-highly-efficient-insecticidal-conotoxins-from-a-transcriptome-based-dataset-of-chinese-tubular-cone-snail
#9
Bingmiao Gao, Chao Peng, Bo Lin, Qin Chen, Junqing Zhang, Qiong Shi
Most previous studies have focused on analgesic and anti-cancer activities for the conotoxins identified from piscivorous and molluscivorous cone snails, but little attention has been devoted to insecticidal activity of conotoxins from the dominant vermivorous species. As a representative vermivorous cone snail, the Chinese tubular cone snail (Conus betulinus) is the dominant Conus species inhabiting the South China Sea. We sequenced related venom transcriptomes from C. betulinus using both the next-generation sequencing and traditional Sanger sequencing technologies, and a comprehensive library of 215 conotoxin transcripts was constructed...
July 6, 2017: Toxins
https://www.readbyqxmd.com/read/28598389/identification-of-a-novel-o-conotoxin-reveals-an-unusual-and-potent-inhibitor-of-the-human-%C3%AE-9%C3%AE-10-nicotinic-acetylcholine-receptor
#10
Shantong Jiang, Han-Shen Tae, Shaoqiong Xu, Xiaoxia Shao, David J Adams, Chunguang Wang
Conotoxins are a pool of disulfide-rich peptide neurotoxins produced by cone snails for predation and defense. They are a rich reservoir of novel ligands for ion channels, neurotransmitter receptors and transporters in the nervous system. In this study, we identified a novel conotoxin component, O-conotoxin GeXXVIIA, from the venom of Conus generalis. The native form of this component is a disulfide-linked homodimer of a 5-Cys-containing peptide. Surprisingly, our electrophysiological studies showed that, in comparison to the folded monomers, the linear peptide of this toxin had the highest inhibitory activity at the human α9α10 nicotinic acetylcholine receptor (nAChR), with an IC50 of 16...
June 9, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28551870/linking-neuroethology-to-the-chemical-biology-of-natural-products-interactions-between-cone-snails-and-their-fish-prey-a-case-study
#11
REVIEW
Baldomero M Olivera, Shrinivasan Raghuraman, Eric W Schmidt, Helena Safavi-Hemami
From a biological perspective, a natural product can be defined as a compound evolved by an organism for chemical interactions with another organism including prey, predator, competitor, pathogen, symbiont or host. Natural products hold tremendous potential as drug leads and have been extensively studied by chemists and biochemists in the pharmaceutical industry. However, the biological purpose for which a natural product evolved is rarely addressed. By focusing on a well-studied group of natural products-venom components from predatory marine cone snails-this review provides a rationale for why a better understanding of the evolution, biology and biochemistry of natural products will facilitate both neuroscience and the potential for drug leads...
May 27, 2017: Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology
https://www.readbyqxmd.com/read/28533165/analgesic-conopeptides-targeting-g-protein-coupled-receptors-reduce-excitability-of-sensory-neurons
#12
REVIEW
Mahsa Sadeghi, Jeffrey R McArthur, Rocio K Finol-Urdaneta, David J Adams
Conotoxins (conopeptides) are a diverse group of peptides isolated from the venom of marine cone snails. Conus peptides modulate pain by interacting with voltage-gated ion channels and G protein-coupled receptors (GPCRs). Opiate drugs targeting GPCRs have long been used, nonetheless, many undesirable side effects associated with opiates have been observed including addiction. Consequently, alternative avenues to pain management are a largely unmet need. It has been shown that various voltage-gated calcium channels (VGCCs) respond to GPCR modulation...
May 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28531118/the-venom-repertoire-of-conus-gloriamaris-chemnitz-1777-the-glory-of-the-sea
#13
Samuel D Robinson, Qing Li, Aiping Lu, Pradip K Bandyopadhyay, Mark Yandell, Baldomero M Olivera, Helena Safavi-Hemami
The marine cone snail Conus gloriamaris is an iconic species. For over two centuries, its shell was one of the most prized and valuable natural history objects in the world. Today, cone snails have attracted attention for their remarkable venom components. Many conotoxins are proving valuable as research tools, drug leads, and drugs. In this article, we present the venom gland transcriptome of C. gloriamaris, revealing this species' conotoxin repertoire. More than 100 conotoxin sequences were identified, representing a valuable resource for future drug discovery efforts...
May 20, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28528674/sodium-channels-and-venom-peptide-pharmacology
#14
Mathilde R Israel, Bryan Tay, Jennifer R Deuis, Irina Vetter
Venomous animals including cone snails, spiders, scorpions, anemones, and snakes have evolved a myriad of components in their venoms that target the opening and/or closing of voltage-gated sodium channels to cause devastating effects on the neuromuscular systems of predators and prey. These venom peptides, through design and serendipity, have not only contributed significantly to our understanding of sodium channel pharmacology and structure, but they also represent some of the most phyla- and isoform-selective molecules that are useful as valuable tool compounds and drug leads...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28479398/isolation-and-characterization-of-conohyal-p1-a-hyaluronidase-from-the-injected-venom-of-conus-purpurascens
#15
Carolina Mӧller, Evan Clark, Helena Safavi-Hemami, Anthony DeCaprio, Frank Marí
Hyaluronidases are ubiquitous enzymes commonly found in venom and their main function is to degrade hyaluran, which is the major glycosaminoglycan of the extracellular matrix in animal tissues. Here we describe the purification and characterization of a 60kDa hyaluronidase found in the injected venom from Conus purpurascens, Conohyal-P1. Using a combined strategy based on transcriptomic and proteomic analysis, we determined the Conohyal-P1 sequence. Conohyal-P1 has conserved consensus catalytic and positioning domain residues characteristic of hyaluronidases and a C-terminus EGF-like domain...
May 4, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28477355/%C3%AE-conotoxins-active-at-%C3%AE-3-containing-nicotinic-acetylcholine-receptors-and-their-molecular-determinants-for-selective-inhibition
#16
REVIEW
Hartmut Cuny, Rilei Yu, Han-Shen Tae, Shiva N Kompella, David J Adams
Neuronal α3-containing nicotinic acetylcholine receptors (nAChRs) in the peripheral nervous system (PNS) and non-neuronal tissues are implicated in a number of severe disease conditions ranging from cancer to cardiovascular diseases and chronic pain. However, despite the physiological characterization of mouse models and cell lines, the precise pathophysiology of nAChRs outside the CNS remains not well understood, in part because there is a lack of subtype-selective antagonists. α-Conotoxins isolated from cone snail venom exhibit characteristic individual selectivity profiles for nAChRs and, therefore, are excellent tools to study the determinants for nAChR-antagonist interactions...
May 6, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28450228/mitogenomic-phylogeny-of-cone-snails-endemic-to-senegal
#17
Samuel Abalde, Manuel J Tenorio, Carlos M L Afonso, Rafael Zardoya
Cone snails attain in Senegal one of their highest peaks of species diversity throughout the continental coast of Western Africa. A total of 15 endemic species have been described, all placed in the genus Lautoconus. While there is ample data regarding the morphology of the shell and the radular tooth of these species, virtually nothing is known regarding the genetic diversity and phylogenetic relationships of one of the most endangered groups of cones. In this work, we determined the complete or near-complete (only lacking the control region) mitochondrial (mt) genomes of 17 specimens representing 11 endemic species (Lautoconus belairensis, Lautoconus bruguieresi, Lautoconus cacao, Lautoconus cloveri, Lautoconus cf...
July 2017: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/28416444/the-pharmacology-of-voltage-gated-sodium-channel-activators
#18
REVIEW
Jennifer R Deuis, Alexander Mueller, Mathilde R Israel, Irina Vetter
Toxins and venom components that target voltage-gated sodium (NaV) channels have evolved numerous times due to the importance of this class of ion channels in the normal physiological function of peripheral and central neurons as well as cardiac and skeletal muscle. NaV channel activators in particular have been isolated from the venom of spiders, wasps, snakes, scorpions, cone snails and sea anemone and are also produced by plants, bacteria and algae. These compounds have provided key insight into the molecular structure, function and pathophysiological roles of NaV channels and are important tools due to their at times exquisite subtype-selectivity...
April 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28411930/marine-envenomation
#19
REVIEW
Kirsten B Hornbeak, Paul S Auerbach
Venomous aquatic animals are hazardous to swimmers, surfers, divers, and fishermen. Exposures include mild stings, bites, abrasions, and lacerations. Severe envenomations can be life threatening. This article reviews common marine envenomations, exploring causative species, clinical presentation, and current treatment recommendations. Recommendations are included for cnidaria, sponges, bristle worms, crown-of-thorns starfish, sea urchins, venomous fish, stingrays, cone snails, stonefish, blue-ringed octopus, and sea snakes...
May 2017: Emergency Medicine Clinics of North America
https://www.readbyqxmd.com/read/28400262/identification-of-short-single-disulfide-containing-contryphans-from-the-venom-of-cone-snails-using-de-novo-mass-spectrometry-based-sequencing-methods
#20
Jayaseelan Benjamin Franklin, Rajaian Pushpabai Rajesh, Nambali Valsalan Vinithkumar, Ramalingam Kirubagaran
We identified 12 short single disulfide-containing conopeptides from the venom of Conus coronatus, C. leopardus, C. lividus and C. zonatus. Interestingly, we detected the shortest contryphan sequence thus far characterized which contains only six amino acid residues. We also identified three distinct contryphan sequences of C. lividus without any proline residues and one sequence with an unusual post-translational modification (bromination of tryptophan). Furthermore, we characterized venom peptides of C...
June 15, 2017: Toxicon: Official Journal of the International Society on Toxinology
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