Contryphan
| Contryphan | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
 | |||||||||||
| Identifiers | |||||||||||
| Symbol | Contryphan_CS | ||||||||||
| Pfam | PF02950 | ||||||||||
| InterPro | IPR011062 | ||||||||||
| PROSITE | PS60027 | ||||||||||
| SCOP2 | 2cco / SCOPe / SUPFAM | ||||||||||
| |||||||||||
The contryphans (conus + tryptophan) are a family of peptides that are active constituents of the potent venom produced by cone snail (genus Conus). The two amino acid cysteine residues in contryphans are linked by a disulfide bond. In addition, contryphans undergo an unusual degree of post-translational modification including epimerization of leucine and tryptophan, tryptophan bromination, amidation of the C-terminus, and proline hydroxylation.[2] In the broader scheme of genetic conotoxin classification, contryphans are members of "Conotoxin Superfamily O2."[3]
Family members
[edit]
Contryphan family members include:
| Peptide | Sequence | Species | Reference |
|---|---|---|---|
| Des(Gly1)contryphan-R | COwEPWC-NH2 | C. radiatus | [4] |
| Contryphan-R | GCOwEPWC-NH2 | Conus radiatus | [4] |
| Bromocontyphan-R | GCOwEPXC-NH2 | C. radiatus | [5] |
| Contryphan-Sm | GCOwQPWC-NH2 | Conus stercusmuscarum | [6] |
| Contryphan-P | GCOwDPWC-NH2 | C. purpurascens | [6] |
| Contryphan-R/Tx | GCOwEPWC-NH2 | Conus textile | [6] |
| Contryphan-Tx | GCOWQPYC-NH2 | Conus textile | [6] |
| Contryphan-Vn | GDCPwKPWC-NH2 | Conus ventricosus | [7] |
| Leu-contryphan-P | GCVlLPWC-OH | Conus purpurascens | [8] |
| Leu-contryphan-Tx | CVlYPWC-NH2 | Conus textile | [6] |
| Glaconryphan-M | NγSγCPWHPWC-NH2 | Conus marmoreus | [2] |
where the sequence abbreviations stand for:
- O = 4-trans-hydroxyproline,
- l = D-leucine, L = L-leucine,
- w = D-tryptophan, W = L-tryptophan,
- γ = gamma-carboxyglutamic acid,
- NH2 = C-terminal amidation
and the remainder of the letters refer to the standard one letter abbreviations for amino acids.
Mechanism of toxicity
[edit]The venom of cone snails cause paralysis of their fish prey. The molecular target has not been determined for all contryphan peptides, however it is known that contryphan-Vn is a Ca2+-dependent K+ channel modulator,[7] while glacontryphan-M is a L-type calcium channel blocker.[2]
References
[edit]- ^ PDB: 1NXN; Eliseo T, Cicero DO, Romeo C, Schininà ME, Massilia GR, Polticelli F, Ascenzi P, Paci M (June 2004). "Solution structure of the cyclic peptide contryphan-Vn, a Ca2+-dependent K+ channel modulator". Biopolymers. 74 (3): 189–98. doi:10.1002/bip.20025. PMID 15150794. S2CID 24487744.
- ^ a b c Hansson K, Ma X, Eliasson L, Czerwiec E, Furie B, Furie BC, Rorsman P, Stenflo J (July 2004). "The first gamma-carboxyglutamic acid-containing contryphan. A selective L-type calcium ion channel blocker isolated from the venom of Conus marmoreus". The Journal of Biological Chemistry. 279 (31): 32453–63. doi:10.1074/jbc.M313825200. PMID 15155730.
- ^ Robinson SD, Norton RS (December 2014). "Conotoxin gene superfamilies". Marine Drugs. 12 (12): 6058–101. doi:10.3390/md12126058. PMC 4278219. PMID 25522317.
- ^ a b Jimenéz EC, Olivera BM, Gray WR, Cruz LJ (November 1996). "Contryphan is a D-tryptophan-containing Conus peptide". The Journal of Biological Chemistry. 271 (45): 28002–5. doi:10.1074/jbc.271.45.28002. PMID 8910408.
- ^ Jimenez EC, Craig AG, Watkins M, Hillyard DR, Gray WR, Gulyas J, Rivier JE, Cruz LJ, Olivera BM (February 1997). "Bromocontryphan: post-translational bromination of tryptophan". Biochemistry. 36 (5): 989–94. doi:10.1021/bi962840p. PMID 9033387.
- ^ a b c d e Jacobsen R, Jimenez EC, Grilley M, Watkins M, Hillyard D, Cruz LJ, Olivera BM (March 1998). "The contryphans, a D-tryptophan-containing family of Conus peptides: interconversion between conformers". The Journal of Peptide Research. 51 (3): 173–9. doi:10.1111/j.1399-3011.1998.tb01213.x. PMID 9531419.
- ^ a b Massilia GR, Schininà ME, Ascenzi P, Polticelli F (November 2001). "Contryphan-Vn: a novel peptide from the venom of the Mediterranean snail Conus ventricosus". Biochemical and Biophysical Research Communications. 288 (4): 908–13. doi:10.1006/bbrc.2001.5833. PMID 11688995.
- ^ Jacobsen RB, Jimenez EC, De la Cruz RG, Gray WR, Cruz LJ, Olivera BM (August 1999). "A novel D-leucine-containing Conus peptide: diverse conformational dynamics in the contryphan family". The Journal of Peptide Research. 54 (2): 93–9. doi:10.1034/j.1399-3011.1999.00093.x. PMID 10461743.
External links
[edit]- Contryphan at the U.S. National Library of Medicine Medical Subject Headings (MeSH)