Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pulicatins A-E, neuroactive thiazoline metabolites from cone snail-associated bacteria.

ABSTRACT: The cone snail Conus pulicarius from the Philippines provides a specific habitat for actinomycetes and other bacteria. A phenotypic screen using primary cultures of mouse dorsal root ganglion neurons revealed that one C. pulicarius associate, Streptomyces sp. CP32, produces a series of natural products that enhance or diminish whole-cell Ca(2+) flux. These compounds include known thiazoline compounds and a series of new derivatives, pulicatins A-E (6-10). Individual compounds were shown to bind to a series of human receptors, with selective binding to the human serotonin 5-HT(2B) receptor. Here, we report the structure elucidation of the new compounds and results of the neurological assays.

SUBMITTER: Lin Z

PROVIDER: S-EPMC2993768 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Pulicatins A-E, neuroactive thiazoline metabolites from cone snail-associated bacteria.

Lin Zhenjian Z Antemano Rowena R RR Hughen Ronald W RW Tianero Ma Diarey B MD Peraud Olivier O Haygood Margo G MG Concepcion Gisela P GP Olivera Baldomero M BM Light Alan A Schmidt Eric W EW

Journal of natural products 20101028 11

The cone snail Conus pulicarius from the Philippines provides a specific habitat for actinomycetes and other bacteria. A phenotypic screen using primary cultures of mouse dorsal root ganglion neurons revealed that one C. pulicarius associate, Streptomyces sp. CP32, produces a series of natural products that enhance or diminish whole-cell Ca(2+) flux. These compounds include known thiazoline compounds and a series of new derivatives, pulicatins A-E (6-10). Individual compounds were shown to bind ...[more]

PMID: 21028889

Similar Datasets

Neuroactive diol and acyloin metabolites from cone snail-associated bacteria.

Project description:The bacterium Gordonia sp. 647W.R.1a.05 was cultivated from the venom duct of the cone snail, Conus circumcisus. The Gordonia sp. organic extract modulated the action potential of mouse dorsal root ganglion neurons. Assay-guided fractionation led to the identification of the new compound circumcin A (1) and 11 known analogs (2-12). Two of these compounds, kurasoin B (7) and soraphinol A (8), were active in a human norepinephrine transporter assay with Ki values of 2575 and 867 nM, respectively. No neuroactivity had previously been reported for compounds in this structural class. Gordonia species have been reproducibly isolated from four different cone snail species, indicating a consistent association between these organisms.

| S-EPMC3779075 | biostudies-literature

Stenotrophomonas-Like Bacteria Are Widespread Symbionts in Cone Snail Venom Ducts.

Project description: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. We found that all venom ducts examined contain diverse 16S rRNA gene sequences bearing closest similarity to Stenotrophomonas bacteria. These sequences represent specific symbionts that live in the lumen of the venom duct, where bioactive venom peptides are synthesized.IMPORTANCE In animals, symbiotic bacteria contribute critically to metabolism. Cone snails are renowned for the production of venoms that are used as medicines and as probes for biological study. In principle, symbiotic bacterial metabolism could either degrade or synthesize active venom components, and previous publications show that bacteria do indeed contribute small molecules to some venoms. Therefore, understanding symbiosis in cone snails will contribute to further drug discovery efforts. Here, we describe an unexpected, specific symbiosis between bacteria and cone snails from around the world.

| S-EPMC5691409 | biostudies-literature

Small Molecules in the Cone Snail Arsenal.

Project description:Cone snails are renowned for producing peptide-based venom, containing conopeptides and conotoxins, to capture their prey. A novel small-molecule guanine derivative with unprecedented features, genuanine, was isolated from the venom of two cone snail species. Genuanine causes paralysis in mice, indicating that small molecules and not just polypeptides may contribute to the activity of cone snail venom.

| S-EPMC4845746 | biostudies-literature

Structural and Functional Analyses of Cone Snail Toxins.

Project description:Cone snails are marine gastropod mollusks with one of the most powerful venoms in nature. The toxins, named conotoxins, must act quickly on the cone snails´ prey due to the fact that snails are extremely slow, reducing their hunting capability. Therefore, the characteristics of conotoxins have become the object of investigation, and as a result medicines have been developed or are in the trialing process. Conotoxins interact with transmembrane proteins, showing specificity and potency. They target ion channels and ionotropic receptors with greater regularity, and when interaction occurs, there is immediate physiological decompensation. In this review we aimed to evaluate the structural features of conotoxins and the relationship with their target types.

| S-EPMC6628382 | biostudies-literature

Non-Peptidic Small Molecule Components from Cone Snail Venoms.

Project description:Venomous molluscs (Superfamily Conoidea) comprise a substantial fraction of tropical marine biodiversity (>15,000 species). Prior characterization of cone snail venoms established that bioactive venom components used to capture prey, defend against predators and for competitive interactions were relatively small, structured peptides (10-35 amino acids), most with multiple disulfide crosslinks. These venom components ("conotoxins, conopeptides") have been widely studied in many laboratories, leading to pharmaceutical agents and probes. In this review, we describe how it has recently become clear that to varying degrees, cone snail venoms also contain bioactive non-peptidic small molecule components. Since the initial discovery of genuanine as the first bioactive venom small molecule with an unprecedented structure, a broad set of cone snail venoms have been examined for non-peptidic bioactive components. In particular, a basal clade of cone snails (Stephanoconus) that prey on polychaetes produce genuanine and many other small molecules in their venoms, suggesting that this lineage may be a rich source of non-peptidic cone snail venom natural products. In contrast to standing dogma in the field that peptide and proteins are predominantly used for prey capture in cone snails, these small molecules also contribute to prey capture and push the molecular diversity of cone snails beyond peptides. The compounds so far characterized are active on neurons and thus may potentially serve as leads for neuronal diseases. Thus, in analogy to the incredible pharmacopeia resulting from studying venom peptides, these small molecules may provide a new resource of pharmacological agents.

| S-EPMC8155685 | biostudies-literature

cone snail LC-MS data water extracts

Project description:the venom duct extracted by pure water and analyzed by LC-MS with a Hilic column

2020-06-17 | MSV000085600 | MassIVE

The mitochondrial genome of the venomous cone snail Conus consors.

Project description:Cone snails are venomous predatory marine neogastropods that belong to the species-rich superfamily of the Conoidea. So far, the mitochondrial genomes of two cone snail species (Conus textile and Conus borgesi) have been described, and these feed on snails and worms, respectively. Here, we report the mitochondrial genome sequence of the fish-hunting cone snail Conus consors and describe a novel putative control region (CR) which seems to be absent in the mitochondrial DNA (mtDNA) of other cone snail species. This possible CR spans about 700 base pairs (bp) and is located between the genes encoding the transfer RNA for phenylalanine (tRNA-Phe, trnF) and cytochrome c oxidase subunit III (cox3). The novel putative CR contains several sequence motifs that suggest a role in mitochondrial replication and transcription.

| S-EPMC3517553 | biostudies-literature

Venomics Reveals Venom Complexity of the Piscivorous Cone Snail, Conus tulipa.

Project description:The piscivorous cone snail Conus tulipa has evolved a net-hunting strategy, akin to the deadly Conus geographus, and is considered the second most dangerous cone snail to humans. Here, we present the first venomics study of C. tulipa venom using integrated transcriptomic and proteomic approaches. Parallel transcriptomic analysis of two C. tulipa specimens revealed striking differences in conopeptide expression levels (2.5-fold) between individuals, identifying 522 and 328 conotoxin precursors from 18 known gene superfamilies. Despite broad overlap at the superfamily level, only 86 precursors (11%) were common to both specimens. Conantokins (NMDA antagonists) from the superfamily B1 dominated the transcriptome and proteome of C. tulipa venom, along with superfamilies B2, A, O1, O3, con-ikot-ikot and conopressins, plus novel putative conotoxins precursors T1.3, T6.2, T6.3, T6.4 and T8.1. Thus, C. tulipa venom comprised both paralytic (putative ion channel modulating ?-, ?-, ?-, ?-) and non-paralytic (conantokins, con-ikot-ikots, conopressins) conotoxins. This venomic study confirms the potential for non-paralytic conotoxins to contribute to the net-hunting strategy of C. tulipa.

| S-EPMC6356538 | biostudies-literature

Venom variation during prey capture by the cone snail, Conus textile.

Project description:Observations of the mollusc-hunting cone snail Conus textile during feeding reveal that prey are often stung multiple times in succession. While studies on the venom peptides injected by fish-hunting cone snails have become common, these approaches have not been widely applied to the analysis of the injected venoms from mollusc-hunters. We have successfully obtained multiple injected venom samples from C. textile individuals, allowing us to investigate venom compositional variation during prey capture. Our studies indicate that C. textile individuals alter the composition of prey-injected venom peptides during single feeding events. The qualitative results obtained by MALDI-ToF mass spectrometry are mirrored by quantitative changes in venom composition observed by reverse-phase high performance liquid chromatography. While it is unclear why mollusc-hunting cone snails inject prey multiple times prior to engulfment, our study establishes for the first time a link between this behavior and compositional changes of the venom during prey capture. Changes in venom composition during hunting may represent a multi-step strategy utilized by these venomous animals to slow and incapacitate prey prior to engulfment.

| S-EPMC4062396 | biostudies-literature

Structures and interactions of insulin-like peptides from cone snail venom.

Project description:The venomous insulin-like peptides released by certain cone snails stimulate hypoglycemic shock to immobilize fish and catch the prey. Compared to human insulin (hIns), the cone snail insulins (Con-Ins) are typically monomeric and shorter in sequence, yet they exhibit moderate hIns-like biological activity. We have modeled six variants of Con-Ins (G3, K1, K2, T1A, T1B, and T2) and carried out explicit-solvent molecular dynamics (MD) simulations of eight types of insulins, two with known structures (hIns and Con-Ins-G1) and six Con-Ins with modeled structures, to characterize key residues of each insulin that interact with the truncated human insulin receptor (μIR). We show that each insulin/μIR complex is stable during explicit-solvent MD simulations and hIns interactions indicate the highest affinity for the "site 1" of IR. The residue contact maps reveal that each insulin preferably interacts with the αCT peptide than the L1 domain of IR. Through analysis of the average nonbonded interaction energy contribution of every residue of each insulin for the μIR, we probe the residues establishing favorable interactions with the receptor. We compared the interaction energy of each residue of every Con-Ins to the μIR and observed that γ-carboxylated glutamate (Gla), His, Thr, Tyr, Tyr/His, and Asn in Con-Ins are favorable substitutions for GluA4, AsnA21, ValB12, LeuB15, GlyB20, and ArgB22 in hIns, respectively. The identified insulin analogs, although lacking the last eight residues of the B-chain of hIns, bind strongly to μIR. Our findings are potentially useful in designing potent fast-acting therapeutic insulin.

| S-EPMC8816879 | 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