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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
April 24, 2017: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/28416444/the-pharmacology-of-voltage-gated-sodium-channel-activators
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28398099/enhancing-the-therapeutic-potential-of-peptide-toxins
#12
REVIEW
Raymond S Norton
Peptide toxins are potent and often exquisitely selective probes of the structure and function of ion channels and receptors, and as such are of significant interest to the pharmaceutical and biotech industries as both therapeutic leads and pharmacological tools. Their progression as clinical candidates, however, faces many of the challenges that are common to peptide drugs generally. Areas covered: The attributes of peptide toxins as therapeutic leads are outlined, as well as some of the limiting factors that have hampered the clinical development of many promising candidates...
June 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28396446/identification-of-a-cono-rfamide-from-the-venom-of-conus-textile-that-targets-asic3-and-enhances-muscle-pain
#13
Catharina Reimers, Cheng-Han Lee, Hubert Kalbacher, Yuemin Tian, Chih-Hsien Hung, Axel Schmidt, Lea Prokop, Silke Kauferstein, Dietrich Mebs, Chih-Cheng Chen, Stefan Gründer
Acid-sensing ion channels (ASICs) are proton-gated Na(+) channels that are expressed throughout the nervous system. ASICs have been implicated in several neuronal disorders, like ischemic stroke, neuronal inflammation, and pathological pain. Several toxins from venomous animals have been identified that target ASICs with high specificity and potency. These toxins are extremely useful in providing protein pharmacophores and to characterize function and structure of ASICs. Marine cone snails contain a high diversity of toxins in their venom such as conotoxins, which are short polypeptides stabilized by disulfide bonds, and conopeptides, which have no or only one disulfide bond...
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28238803/discovery-and-characterization-of-eiib-a-new-%C3%AE-conotoxin-from-conus-ermineus-venom-by-nachrs-affinity-capture-monitored-by-maldi-tof-tof-mass-spectrometry
#14
Julien Echterbille, Nicolas Gilles, Romulo Araóz, Gilles Mourier, Muriel Amar, Denis Servent, Edwin De Pauw, Loic Quinton
Animal toxins are peptides that often bind with remarkable affinity and selectivity to membrane receptors such as nicotinic acetylcholine receptors (nAChRs). The latter are, for example, targeted by α-conotoxins, a family of peptide toxins produced by venomous cone snails. nAChRs are implicated in numerous physiological processes explaining why the design of new pharmacological tools and the discovery of potential innovative drugs targeting these receptor channels appear so important. This work describes a methodology developed to discover new ligands of nAChRs from complex mixtures of peptides...
February 24, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28216409/structure-and-activity-of-contryphan-vc2-importance-of-the-d-amino-acid-residue
#15
Stephen B Drane, Samuel D Robinson, Christopher A MacRaild, Sandeep Chhabra, Balasubramanyam Chittoor, Rodrigo A V Morales, Eleanor W W Leung, Alessia Belgi, Samuel S Espino, Baldomero M Olivera, Andrea J Robinson, David K Chalmers, Raymond S Norton
In natural proteins and peptides, amino acids exist almost invariably as l-isomers. There are, however, several examples of naturally-occurring peptides containing d-amino acids. In this study we investigated the role of a naturally-occurring d-amino acid in a small peptide identified in the transcriptome of a marine cone snail. This peptide belongs to a family of peptides known as contryphans, all of which contain a single d-amino acid residue. The solution structure of this peptide was solved by NMR, but further investigations with molecular dynamics simulations suggest that its solution behaviour may be more dynamic than suggested by the NMR ensemble...
February 17, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28152596/contryphan-genes-and-mature-peptides-in-the-venom-of-nine-cone-snail-species-by-transcriptomic-and-mass-spectrometric-analysis
#16
Marimuthu Vijayasarathy, Soorej M Basheer, Jayaseelan Benjamin Franklin, Padmanabhan Balaram
The occurrence of contryphans, a class of single-disulfide-bond-containing peptides, is demonstrated by the analysis of the venom of nine species of cone snails. Ten full gene sequences and two partial gene sequences coding for contryphan precursor proteins have been identified by next-generation sequencing and compared with available sequences. The occurrence of mature peptides in isolated venom has been demonstrated by LC-ESI-MS/MS analysis. De novo sequencing of reduced, alkylated contryphans from C. frigidus and C...
February 3, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28148828/ocean-acidification-alters-predator-behaviour-and-reduces-predation-rate
#17
Sue-Ann Watson, Jennifer B Fields, Philip L Munday
Ocean acidification poses a range of threats to marine invertebrates; however, the emerging and likely widespread effects of rising carbon dioxide (CO2) levels on marine invertebrate behaviour are still little understood. Here, we show that ocean acidification alters and impairs key ecological behaviours of the predatory cone snail Conus marmoreus Projected near-future seawater CO2 levels (975 µatm) increased activity in this coral reef molluscivore more than threefold (from less than 4 to more than 12 mm min(-1)) and decreased the time spent buried to less than one-third when compared with the present-day control conditions (390 µatm)...
February 2017: Biology Letters
https://www.readbyqxmd.com/read/27941639/evolution-of-the-cytolytic-pore-forming-proteins-actinoporins-in-sea-anemones
#18
Jason Macrander, Marymegan Daly
Sea anemones (Cnidaria, Anthozoa, and Actiniaria) use toxic peptides to incapacitate and immobilize prey and to deter potential predators. Their toxin arsenal is complex, targeting a variety of functionally important protein complexes and macromolecules involved in cellular homeostasis. Among these, actinoporins are one of the better characterized toxins; these venom proteins form a pore in cellular membranes containing sphingomyelin. We used a combined bioinformatic and phylogenetic approach to investigate how actinoporins have evolved across three superfamilies of sea anemones (Actinioidea, Metridioidea, and Actinostoloidea)...
December 8, 2016: Toxins
https://www.readbyqxmd.com/read/27916464/subtype-specific-block-of-voltage-gated-k-channels-by-%C3%AE-conopeptides
#19
Enrico Leipold, Florian Ullrich, Markus Thiele, Alesia A Tietze, Heinrich Terlau, Diana Imhof, Stefan H Heinemann
The neurotoxic cone snail peptide μ-GIIIA specifically blocks skeletal muscle voltage-gated sodium (NaV1.4) channels. The related conopeptides μ-PIIIA and μ-SIIIA, however, exhibit a wider activity spectrum by also inhibiting the neuronal NaV channels NaV1.2 and NaV1.7. Here we demonstrate that those μ-conopeptides with a broader target range also antagonize select subtypes of voltage-gated potassium channels of the KV1 family: μ-PIIIA and μ-SIIIA inhibited KV1.1 and KV1.6 channels in the nanomolar range, while being inactive on subtypes KV1...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27826319/in-the-picture-disulfide-poor-conopeptides-a-class-of-pharmacologically-interesting-compounds
#20
REVIEW
Eline K M Lebbe, Jan Tytgat
During evolution, nature has embraced different strategies for species to survive. One strategy, applied by predators as diverse as snakes, scorpions, sea anemones and cone snails, is using venom to immobilize or kill a prey. This venom offers a unique and extensive source of chemical diversity as it is driven by the evolutionary pressure to improve prey capture and/or to protect their species. Cone snail venom is an example of the remarkable diversity in pharmacologically active small peptides that venoms can consist of...
2016: Journal of Venomous Animals and Toxins Including Tropical Diseases
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