Pharmacological families
Conotoxins, the disulfide rich conopeptides, are classified according to three schemes: the similarities between the ER signal sequence of the conotoxin precursors (gene superfamilies), the cysteine patterns of conotoxin mature peptide regions (cysteine frameworks), and the specificities to pharmacological targets (pharmacological families). This page provides a brief introduction to the pharmacological families and a list of the pharmacological families used in ConoServer. The two other classification schemes are detailed in separate pages accessible from the menu on the left. A more comprehensive discussion of the conopeptide classification schemes can be found in Kaas et al. Toxicon 2010 [1].
Pharmacological families are defined in ConoServer as conopeptides sharing the same receptor specificities, which include the type of targeted receptors and the physiological activity (agonist, antagonist and other physiologically measurable characteristics). The pharmacological families are noted using a greek letter.
Some differences exist between the nomenclature used for pharmacological families in the literature and in ConoServer. For example, the information regarding binding sites are not included in the definition used in ConoServer, and therefore the αA family used in the literature is included in the α pharmacological family in ConoServer. Information on the binding sites are difficult to obtain and are here considered as inadequate for a general classification of conopeptide pharmacological effects. Binding site informations are indicated as notes in ConoServer. Differences between the literature and ConoServer definitions only concern a small number of peptides, as detailed in Kaas et al. Toxicon 2010 [1].
| Family | Definition | Representative toxin(s) |
Reference |
|---|---|---|---|
| α (alpha) | Nicotinic acetylcholine receptors (nAChR) | GI | Gray,W.R. et al. (1981) J. Biol. Chem. 256:4734-4740 |
| γ (gamma) | Neuronal pacemaker cation currents (inward cation current) | PnVIIA, TxVIIA | Fainzilber,M. et al. (1998) Biochemistry 37:1470-1477 |
| δ (delta) | Voltage-gated Na channels (agonist, delay inactivation) | TxVIA | Fainzilber,M. et al. (1991) Eur. J. Biochem. 202:589-595 |
| ε (epsilon) | Presynaptic Ca channels or G protein-coupled presynaptic receptors | TxVA | Rigby,A.C. et al. (1999) Proc. Natl. Acad. Sci. U.S.A. 96:5758-5763 |
| ι (iota) | Voltage-gated Na channels (agonist, no delayed inactivation) | RXIA | Buczek,O. et al. (2007) Biochemistry 46:9929-9940 |
| κ (kappa) | Voltage-gated K channels (blocker) | PVIIA | Terlau,H. et al. (1996) Nature 381:148-151 |
| μ (mu) | Voltage-gated Na channels (antagonist, blocker) | GIIIA | Cruz,L.J. et al. (1985) J. Biol. Chem. 260:9280-9288 |
| ρ (rho) | Alpha1-adrenoceptors (GPCR) | TIA | Sharpe,I.A. et al. (2001) Nat. Neurosci. 4:902-907 |
| σ (sigma) | Serotonin-gated ion channels 5-HT3 | GVIIIA | England,L.J. et al. (1998) Science 281:575-578 |
| τ (tau) | Somatostatin receptor | CnVA | Petrel,C. et al. (2013) Biochem. Pharmacol. |
| χ (chi) | Neuronal noradrenaline transporter | MrIA, CMrVIA | Sharpe,I.A. et al. (2001) Nat. Neurosci. 4:902-907 |
| ω (omega) | Voltage-gated Ca channels (blocker) | GVIA | Kerr,L.M. and Yoshikami,D. (1984) Nature 308:282-284 |
| [1] | Kaas,Q. et al. (2010) Toxicon 55:1491-1509 |
Please cite:
Kaas Q, Yu R, Jin AH, Dutertre S and Craik DJ. ConoServer: updated content, knowledge, and discovery tools in the conopeptide database. Nucleic Acids Research (2012) 40(Database issue):D325-30
Kaas Q, Westermann JC, Halai R, Wang CK and Craik DJ. ConoServer, a database for conopeptide sequences and structures. Bioinformatics (2008) 24(3):445-6
Kaas Q, Yu R, Jin AH, Dutertre S and Craik DJ. ConoServer: updated content, knowledge, and discovery tools in the conopeptide database. Nucleic Acids Research (2012) 40(Database issue):D325-30
Kaas Q, Westermann JC, Halai R, Wang CK and Craik DJ. ConoServer, a database for conopeptide sequences and structures. Bioinformatics (2008) 24(3):445-6
ConoServer is managed at the Institute of Molecular Bioscience IMB, Brisbane, Australia.
The database and computational tools found on this website may be used for academic research only, provided that it is referred to ConoServer, the database of conotoxins (http://www.conoserver.org) and the above reference is cited. For any other use please contact David Craik (d.craik@imb.uq.edu.au).
Contacts:
David Craik
Quentin Kaas
Last updated: Monday 30 January 2023