Contryphan

Contryphan
NMR structure of Contryphan-Vn. The peptide backbone is depicted by a curved tube while the amino acid side-chains are represented by capped sticks. Carbon atoms are colored grey, nitrogen atoms blue, oxygen atoms red, and sulfur atoms yellow.
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Identifiers
SymbolContryphan_CS
PfamPF02950
InterProIPR011062
PROSITEPS60027
SCOP22cco / SCOPe / SUPFAM
Available protein structures:
PDB  1dfy ​, 1dfz​ , 1dg0​ , 1nxn​ , 1qfb​ IPR011062 PF02950 (ECOD; PDBsum)  
AlphaFold

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. In the broader scheme of genetic conotoxin classification, contryphans are members of "Conotoxin Superfamily O2."

Family members

Conus textile, which produces contryphans

Contryphan family members include:

Peptide Sequence Species Reference
Des(Gly1)contryphan-R COwEPWC-NH2 C. radiatus
Contryphan-R GCOwEPWC-NH2 Conus radiatus
Bromocontyphan-R GCOwEPXC-NH2 C. radiatus
Contryphan-Sm GCOwQPWC-NH2 Conus stercusmuscarum
Contryphan-P GCOwDPWC-NH2 C. purpurascens
Contryphan-R/Tx GCOwEPWC-NH2 Conus textile
Contryphan-Tx GCOWQPYC-NH2 Conus textile
Contryphan-Vn GDCPwKPWC-NH2 Conus ventricosus
Leu-contryphan-P GCVlLPWC-OH Conus purpurascens
Leu-contryphan-Tx CVlYPWC-NH2 Conus textile
Glaconryphan-M NγSγCPWHPWC-NH2 Conus marmoreus

where the sequence abbreviations stand for:

and the remainder of the letters refer to the standard one letter abbreviations for amino acids.

Mechanism of toxicity

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, while glacontryphan-M is a L-type calcium channel blocker.

References

  1. ↑ 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.
  2. 1 2 3 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.
  3. ↑ Robinson SD, Norton RS (December 2014). "Conotoxin gene superfamilies". Marine Drugs. 12 (12): 6058–101. doi:10.3390/md12126058. PMC 4278219. PMID 25522317.
  4. 1 2 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.
  5. ↑ 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.
  6. 1 2 3 4 5 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.
  7. 1 2 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. Bibcode:2001BBRC..288..908M. doi:10.1006/bbrc.2001.5833. PMID 11688995.
  8. ↑ 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.