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Protein Domain : Conotoxin, omega-type, conserved site

Primary Identifier  IPR012321 Type  Conserved_site
Short Name  Conotoxin_omega-typ_CS
description  Cone snail toxins, conotoxins, are small neurotoxic peptides with disulphide connectivity that target ion-channels or G-protein coupled receptors. Based on the number and pattern of disulphide bonds and biological activities, conotoxins can be classified into several families []. Omega, delta and kappa families of conotoxins have a knottin or inhibitor cysteine knot scaffold. The knottin scaffold is a very special disulphide-through-disulphide knot, in which the III-VI disulphide bond crosses the macrocycle formed by two other disulphide bonds (I-IV and II-V) and the interconnecting backbone segments, where I-VI indicates the six cysteine residues starting from the N terminus.Conotoxins represent a unique arsenal of neuropharmacologically active peptides that have been evolutionarily tailored to afford unprecedented andexquisite selectivity for a wide variety of ion-channel subtypes. The toxinsderived from cone snails are currently being investigated for the treatment ofchronic pain, epilepsy, cardiovascular diseases, psychiatric and movementdisorders, spasticity, cancer, and stroke, as well as an anesthetic agent. Several potential analgesic and anti-inflammatory peptides from conotoxin family have been identified and patented [, ]:Conus magus (Magus cone) (Magician's cone snail) omega-conotoxin MVIIa (Ziconotide) is used for the treatment of chronic pain.Conus catus (Cat cone) omega-conotoxin CVID is tested for treating severe morphine-resistant pain stress.Conus geographus (Geography cone) (Nubecula geographus) omega-conotoxin GVIA may exert antagonistic effects against beta-endorphin induced anti-nociception.The cysteine arrangements [C-C-CC-C-C]are the same for the omega and delta families, even though omega conotoxins are calcium channel blockers, whereas delta conotoxins delay the inactivation of sodium channels. The disulphide bonding network as well as specific amino acids in inter-cysteine loops provide the specificity of conotoxins []. Two signature patterns were developed for the omega and delta conotoxin families. The patterns each include six conserved cysteines thought to be important for the maintenance of the tertiary structure of the conotoxins. This entry represents the omega-conotoxins.

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