Conus venom peptides, receptor and ion channel targets, and drug design: 50 million years of neuropharmacology

Journal ArticleThe predatory cone snails (Conus) are among the most successful living marine animals (~500 living species). Each Conus species is a specialist in neuropharmacology, and uses venom to capture prey, to escape from and defend against predators and possibly to deter competitors. An individual cone snail's venom contains a diverse mixture of pharmacological agents, mostly small, structurally constrained peptides (conotoxins). Individual peptides are selectively targeted to a specific isoform of receptor or ion channel

Subfamily Turrinae in the Philippines: the genus Turris (Roding, 1798)

Journal ArticleMarine gastropods of the family Turridae, commonly known as turrids, comprise the largest living group of venomous snails. The taxonomy of this group, however, has been generally neglected. In this work, the genus Tunis (Roding 1798) is discussed. Out of more than 200 different turrid genera, this genus comprises some of the largest and most distinctive living turrid species. The last comprehensive treatment of this particular genus (Powell 1964) identified seven species from the Philippines. In this paper, twelve distinct species of Turns found in the Philippine waters are recognized. Four new species are described: TurrJs dollyae, T. normandavidsoni, T. pagasa and T. totiphyllis. Insufficient material makes it premature to conclude whether three additional distinctive Turn's forms are separate species, or unusual varieties of other species. The taxonomic status of the genus Turns and its relationship to other Turrinae is further discussed. Alternative hypotheses regarding the evolutionary origins of this group are also considered. In addition, two species of Gemmula, with particular affinities for species clades in Turris are noted: one is a new species and one is a renamed homony

Conus peptides: biodiversity-based discovery and exogenomics

Journal ArticleThe venoms of the ~700 species of predatory cone snails (genus Conus) are being systematically characterized. Each Conus species contains 100-200 small, highly structured venom peptides (colloquially known as conotoxins), which are synthesized and secreted in a venom duct (for overviews, see Refs. 1-3). The biomedical potential of these small venom peptides is now well established; recent developments are summarized below. Additionally, the genetic basis and biological rationale for Conus peptide diversity is addressed

Inhibition of Escherichia coli chemotaxis by omega-conotoxin, a calcium ion channel blocker

Escherichia coli chemotaxis was inhibited by omega-conotoxin, a calcium ion channel blocker. With Tris-EDTA-permeabilized cells, nanomolar levels of omega-conotoxin inhibited chemotaxis without loss of motility. Cells treated with omega-conotoxin swam with a smooth bias, i.e., tumbling was inhibited

Novel Conus peptide ligand for K+ channels

Journal ArticleVoltage-gated ion channels determine the membrane excitability of cells. Although many Conus peptides that interact with voltage-gated Na+ and Ca2+ channels have been characterized, relatively few have been identified that interact with K+ channels. We describe a novel Conus peptide that interacts with the Shaker K+ channel, қM-conotoxin RIIIK from Conus radiatus

Pyridine nucleotide cycle: studies in Escherichia coli and the human cell line D98/AH2

Journal ArticleDifferent metabolic steps comprise the pyridine nucleotide cycles in Escherichia coli and in the human cell line HeLa D98/AH2. An analysis of the "P-labeling patterns in vivo reveals that in E. coli, pyrophosphate bond cleavage of intracellular NAD predominates, while in the human cell line, cleavage of the nicotinamide ribose bond predominates

Pyridine nucleotide metabolism in Escherichia coli. II. Niacin starvation

Journal ArticleThe effect of niacin starvation has been studied in a niacin-requiring auxotroph of Escherichia coli. If a culture is totally deprived of niacin, cells continue to divide until the total pyridine nucleotide content has fallen from 1.9 X 10^6 to 1.2 X 10^5 molecules per cell. During starvation, the relative proportion of the pyridine nucleotides changes greatly: the TPN: DPN ratio increases from 0.30 to over 2.0 and nicotinic acid mononucleotide accumulates until it is present at concentrations comparable to DPN

Differential targeting of nicotinic acetylcholine receptors by novel αA-conotoxins

Journal ArticleWe describe the isolation and characterization of two peptide toxins from Conus ermineus venom targeted to nicotinic acetylcholine receptors (nAChRs). The peptide structures have been confirmed by mass spectrometry and chemical synthesis. In contrast to the 12-18 residue, 4 Cys-containing α-conotoxins, the new toxins have 30 residues and 6 Cys residues

Conotoxins

Journal ArticleMany successful animal and plant families have developed distinctive biochemical strategies; one of the more unusual examples is found in a group of marine gastropods, the cone snails (Conus) (1). These animals have evolved a specialized biochemistry of small constrained peptides, the conotoxins. These peptides are the direct translation products of genes (2). However, because they are small enough for direct chemical synthesis and sufficiently constrained for three-dimensional conformation determination, conotoxins bridge protein chemistry and molecular genetics. Furthermore, the strategy that the cone snails have evolved over millions of years for the generation and design of an enormous array of small peptide ligands, each with high affinity and specificity for a particular receptor protein target, may be adaptable for use in vitro

Post-translational amino acid isomerization: a functionally important D-amino acid in an excitatory peptide

Journal ArticleThe post-translational modification of an L- to a D-amino acid has been documented in relatively few gene products, mostly in small peptides under 10 amino acids in length. In this report, we demonstrate that a 46-amino acid polypeptide toxin has one D-phenylalanine at position 44, and that the epimerization from an L-Phe to a D-Phe has a dramatic effect on the excitatory effects of the peptide