{PDOC60027} {PS60027; CONTRYPHAN} {BEGIN} ******************************* * Contryphan family signature * ******************************* Contryphans are a family of short disulfide constrained peptides isolated from various species of cone shell. They constitute a group of conopeptides that are known to contain an unusual density of post-translational modifications including tryptophan bromination, amidation of the C-terminal residue, leucine, and tryptophan isomerization, proline hydroxylation and glutamic acid gamma-carboxylation [1-5]. Contryphans share the conserved sequence motif, CP*(D-W or D-L)XPWC, that includes a tryptophan or leucine in the D-conformation, a disulfide bond between the two cysteines, and in some cases hydroxylation of the proline preceding the D-Trp residue, Pro*. The N-terminal Cys-Pro/Hyp (hydroxyproline) peptide bond exhibits cis-trans isomerization in most contryphans; however the more abundant cis isomer is believed to be the functionally relevant conformer. The contryphan fold consists of a seven residue loop stabilized by a disulfide bridge (see and ) [1,3,5]. This family includes: - Contryphan-P and Leu-contryphan-P from Conus purpurascens (Purple cone). - Contryphan-Tx, contryphan-R/Tx and Leu-contryphan-Tx from Conus textile (Cloth-of-gold cone) [2]. - Glacontryphan-M from Conus marmoreus (Marble cone), a calcium-dependent inhibitor of L-type voltage-gated Ca2+ channels [4,5]. - Contryphan from Conus radiatus (Rayed cone). - Contryphan-Sm from Conus stercusmuscarum (Fly-specked cone) [1]. - Contryphan-Vn from Conus ventricosus (Mediterranean cone) [3]. We have developed a pattern that contains the two conserved cysteines. -Conserved pattern: C-[PV]-[WL]-x-P-[YW]-C-x(0,1)> [The 2 C's are involved in disulfide bonds] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Expert(s) to contact by email: Ramakumar S.; ramak@physics.iisc.ernet.in -Last update: March 2008 / Pattern revised. [ 1] Pallaghy P.K., He W., Jimenez E.C., Olivera B.M., Norton R.S. "Structures of the contryphan family of cyclic peptides. Role of electrostatic interactions in cis-trans isomerism." Biochemistry 39:12845-12852(2000). PubMed=11041849 [ 2] Jimenez E.C., Watkins M., Juszczak L.J., Cruz L.J., Olivera B.M. "Contryphans from Conus textile venom ducts." Toxicon 39:803-808(2001). PubMed=11137539 [ 3] Eliseo T., Cicero D.O., Romeo C., Schinina M.E., Massilia G.R., Polticelli F., Ascenzi P., Paci M. "Solution structure of the cyclic peptide contryphan-Vn, a Ca2+-dependent K+ channel modulator." Biopolymers 74:189-198(2004). PubMed=15150794; DOI=10.1002/bip.20025 [ 4] Hansson K., Ma X., Eliasson L., Czerwiec E., Furie B., Furie B.C., Rorsman P., Stenflo J. "The first gamma-carboxyglutamic acid-containing contryphan. A selective L-type calcium ion channel blocker isolated from the venom of Conus marmoreus." J. Biol. Chem. 279:32453-32463(2004). PubMed=15155730; DOI=10.1074/jbc.M313825200 [ 5] Grant M.A., Hansson K., Furie B.C., Furie B., Stenflo J., Rigby A.C. "The metal-free and calcium-bound structures of a gamma-carboxyglutamic acid-containing contryphan from Conus marmoreus, glacontryphan-M." J. Biol. Chem. 279:32464-32473(2004). PubMed=15155731; DOI=10.1074/jbc.M313826200 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}