Contryphan

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]

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.[1] .
Identifiers
Symbol	Contryphan_CS
Pfam	PF02950
InterPro	IPR011062
PROSITE	PS60027
SCOP2	2cco / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary PDB 1dfy ​, 1dfz​ , 1dg0​ , 1nxn​ , 1qfb​

Family members

Conus textile, which produces contryphans

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

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]