scholarly journals A vasopressin/oxytocin-related conopeptide with γ-carboxyglutamate at position 8

2007 ◽  
Vol 404 (3) ◽  
pp. 413-419 ◽  
Author(s):  
Carolina Möller ◽  
Frank Marí
Keyword(s):  
Calcium Binding ◽  
Structural Changes ◽  
Complex Mixture ◽  
Snail Species ◽  
Cone Snail ◽  
Basic Residue ◽  
Western Atlantic ◽  
Neuroactive Peptides ◽  
Cone Snails ◽  
Multifunctional Peptides

Vasopressins and oxytocins are homologous, ubiquitous and multifunctional peptides present in animals. Conopressins are vasopressin/oxytocin-related peptides that have been found in the venom of cone snails, a genus of marine predatory molluscs that envenom their prey with a complex mixture of neuroactive peptides. In the present paper, we report the purification and characterization of a unique conopressin isolated from the venom of Conus villepinii, a vermivorous cone snail species from the western Atlantic Ocean. This novel peptide, designated γ-conopressin-vil, has the sequence CLIQDCPγG* (γ is γ-carboxyglutamate and * is C-terminal amidation). The unique feature of this vasopressin/oxytocin-like peptide is that the eighth residue is γ-carboxyglutamate instead of a neutral or basic residue; therefore it could not be directly classified into either the vasopressin or the oxytocin peptide families. Nano-NMR spectroscopy of the peptide isolated directly from the cone snails revealed that the native γ-conopressin-vil undergoes structural changes in the presence of calcium. This suggests that the peptide binds calcium, and the calcium-binding process is mediated by the γ-carboxyglutamate residue. However, the negatively charged residues in the sequence of γ-conopressin-vil may mediate calcium binding by a novel mechanism not observed in other peptides of this family.

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

2017 ◽  
Vol 83 (23) ◽  
Author(s):  
Joshua P. Torres ◽  
Maria Diarey Tianero ◽  
Jose Miguel D. Robes ◽  
Jason C. Kwan ◽  
Jason S. Biggs ◽  
...  
Keyword(s):  
16S Rrna ◽  
16S Rrna Gene ◽  
Marine Invertebrates ◽  
The Philippines ◽  
Biological Study ◽  
Snail Species ◽  
Rrna Gene ◽  
Cone Snail ◽  
The World ◽  
Cone Snails

ABSTRACT 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.

scholarly journals Diverse Cone-Snail Species Harbor Closely Related Streptomyces Species with Conserved Chemical and Genetic Profiles, Including Polycyclic Tetramic Acid Macrolactams

2017 ◽  
Vol 8 ◽  
Author(s):  
Michelle Quezada ◽  
Cuauhtemoc Licona-Cassani ◽  
Pablo Cruz-Morales ◽  
Angela A. Salim ◽  
Esteban Marcellin ◽  
...  
Keyword(s):  
Snail Species ◽  
Cone Snail ◽  
Tetramic Acid ◽  
Streptomyces Species ◽  
Genetic Profiles

scholarly journals Diversity of Conopeptides and Their Precursor Genes of Conus Litteratus

Marine Drugs ◽  
2020 ◽  
Vol 18 (9) ◽  
pp. 464
Author(s):  
Xinjia Li ◽  
Wanyi Chen ◽  
Dongting Zhangsun ◽  
Sulan Luo
Keyword(s):  
Codon Usage ◽  
Codon Usage Bias ◽  
Major Type ◽  
Snail Species ◽  
Cone Snail ◽  
Codon Preference ◽  
Specific Receptors ◽  
Marine Peptide ◽  
Simple Sequence ◽  
Repeat Detection

The venom of various Conus species is composed of a rich variety of unique bioactive peptides, commonly referred to as conotoxins (conopeptides). Most conopeptides have specific receptors or ion channels as physiologically relevant targets. In this paper, high-throughput transcriptome sequencing was performed to analyze putative conotoxin transcripts from the venom duct of a vermivorous cone snail species, Conus litteratus native to the South China Sea. A total of 128 putative conotoxins were identified, most of them belonging to 22 known superfamilies, with 43 conotoxins being regarded as belonging to new superfamilies. Notably, the M superfamily was the most abundant in conotoxins among the known superfamilies. A total of 15 known cysteine frameworks were also described. The largest proportion of cysteine frameworks were VI/VII (C-C-CC-C-C), IX (C-C-C-C-C-C) and XIV (C-C-C-C). In addition, five novel cysteine patterns were also discovered. Simple sequence repeat detection results showed that di-nucleotide was the major type of repetition, and the codon usage bias results indicated that the codon usage bias of the conotoxin genes was weak, but the M, O1, O2 superfamilies differed in codon preference. Gene cloning indicated that there was no intron in conotoxins of the B1- or J superfamily, one intron with 1273–1339 bp existed in a mature region of the F superfamily, which is different from the previously reported gene structure of conotoxins from other superfamilies. This study will enhance our understanding of conotoxin diversity, and the new conotoxins discovered in this paper will provide more potential candidates for the development of pharmacological probes and marine peptide drugs.

scholarly journals Sequential Structural Changes upon Zinc and Calcium Binding to Metal-free Concanavalin A

1996 ◽  
Vol 271 (27) ◽  
pp. 16144-16150 ◽  
Author(s):  
Julie Bouckaert ◽  
Freddy Poortmans ◽  
Lode Wyns ◽  
Remy Loris
Keyword(s):  
Concanavalin A ◽  
Calcium Binding ◽  
Structural Changes ◽  
Metal Free

The NMR angle on troponin C

1998 ◽  
Vol 76 (2-3) ◽  
pp. 302-312 ◽  
Author(s):  
Stéphane M Gagné ◽  
Monica X Li ◽  
Ryan T McKay ◽  
Brian D Sykes
Keyword(s):  
Calcium Binding ◽  
Structural Changes ◽  
Regulatory Protein ◽  
Protein Nmr ◽  
Troponin C ◽  
Structural Studies ◽  
Cardiac System ◽  
Helical Proteins ◽  
Central Paradigm ◽  
Concomitant Exposure

The calcium-induced structural changes in the skeletal muscle regulatory protein troponin C involve a transition from a closed to an open structure with the concomitant exposure of a large hydrophobic interaction site for target proteins. NMR solution structural studies have served to define this conformational change and elucidate the mechanism of the linkage between calcium binding and the induced structural changes. These structural movements are described in terms of interhelical angles in these largely helical proteins. Oddly, the most recent structure of the cardiac system challenges the central paradigm because the calcium-bound structures are not open. The kinetics, energetics, and dynamics of these proteins have also been investigated using NMR.Key words: troponin C, calcium binding protein, NMR, structure, energetics.

Monitoring Conformational Changes in Protein Complexes Using Chemical Cross-Linking and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry: The Effect of Calcium Binding on the Calmodulin—Melittin Complex

2007 ◽  
Vol 13 (4) ◽  
pp. 281-290 ◽  
Author(s):  
Petr Novak ◽  
Vladimir Havlicek ◽  
Peter J. Derrick ◽  
Kyle A. Beran ◽  
Sajid Bashir ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Fourier Transform ◽  
Conformational Changes ◽  
Calcium Binding ◽  
Cyclotron Resonance ◽  
Structural Changes ◽  
Cross Linking ◽  
Ion Cyclotron Resonance ◽  
Ion Cyclotron ◽  
Chemical Cross Linking

Calmodulin is an EF hand calcium binding protein. Its binding affinities to various protein/peptide targets often depend on the conformational changes induced by the binding of calcium. One such target is melittin, which binds tightly to calmodulin in the presence of calcium, and inhibits its function. Chemical cross-linking combined with Fourier transform ion cyclotron resonance mass spectrometry has been employed to investigate the coordination of calmodulin and melittin in the complex at different concentrations of calcium. This methodology can be used to monitor structural changes in proteins induced by ligand binding and to study the effects these changes have on non-covalent interactions between proteins. Cross-linking results indicate that the binding place of the first melittin in the calcium-free calmodulin form is the same as in the calcium-loaded calmodulin/melittin complex.

scholarly journals Calcium regulates tertiary structure and enzymatic activity of human endometase/matrilysin-2 and its role in promoting human breast cancer cell invasion

2007 ◽  
Vol 403 (1) ◽  
pp. 31-42 ◽  
Author(s):  
Seakwoo Lee ◽  
Hyun I. Park ◽  
Qing-Xiang Amy Sang
Keyword(s):  
Breast Cancer ◽  
Enzymatic Activity ◽  
Binding Site ◽  
Calcium Binding ◽  
Human Breast Cancer ◽  
Structural Changes ◽  
Human Breast Cancer Cell ◽  
Human Breast ◽  
Calcium Binding Site ◽  
High Affinity

Human MMP-26 (matrix metalloproteinase-26) (also known as endometase or matrilysin-2) is a putative biomarker for human carcinomas of breast, prostate and other cancers of epithelial origin. Calcium modulates protein structure and function and may act as a molecular signal or switch in cells. The relationship between MMPs and calcium has barely been studied and is absent for MMP-26. We have investigated the calcium-binding sites and the role of calcium in MMP-26. MMP-26 has one high-affinity and one low-affinity calcium binding site. High-affinity calcium binding was restored at physiologically low calcium conditions with a calcium-dissociation constant of 63 nM without inducing secondary and tertiary structural changes. High-affinity calcium binding protects MMP-26 against thermal denaturation. Mutants of this site (D165A or E191A) lose enzymatic activity. Low-affinity calcium binding was restored at relatively high calcium concentrations and showed a Kd2 (low-affinity calcium-dissociation constant) value of 120 μM, which was accompanied with the recovery of enzymatic activity reversibly and tertiary structural changes, but without secondary structural rearrangements. Mutations at the low-affinity calcium-binding site (C3 site), K189E or D114A, induced enhanced affinity for the Ca2+ ion or an irreversible loss of enzymatic activity triggered by low-affinity calcium binding respectively. Mutation at non-calcium-binding site (V184D at C2 site) showed that C2 is not a true calcium-binding site. Observations from homology-modelled mutant structures correlated with these experimental results. A human breast cancer cell line, MDA-MB-231, transfected with wild-type MMP-26 cDNA showed a calcium-dependent invasive potential when compared with controls that were transfected with an inactive form of MMP-26 (E209A). Calcium-independent high invasiveness was observed in the K189E mutant MDA-MB-231 cell line.

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