Conotoxin 1937838 222263560 2008-06-28T11:55:00Z SpBot 7016748 robot Adding: [[de:Conotoxine]] {{Pfam_box | Symbol = Alpha conotoxin | Name = | image = alpha-Conotoxin from Conus pennaceus 1AKG.png | width = | caption = α-Conotoxin PnIB from ''C. pennaceus'', disulfide bonds shown in yellow. From the University of Michigan's [[Orientations of Proteins in Membranes database]], {{PDB|1AKG}}. | Pfam= PF07365 | InterPro= IPR009958 | SMART= | Prosite = | SCOP = 1mii | TCDB = | OPM family= | OPM protein= 1akg | PDB= {{PDB3|1akg}} :45-60 {{PDB3|2ak0}}A:22-38 {{PDB3|1m2c}} :22-37 {{PDB3|1mii}}A:22-37 {{PDB3|2ajw}}A:22-38 {{PDB3|1qmw}}A:50-62 {{PDB3|1hje}}A:50-62 {{PDB3|1ul2}}A:21-36 }} {{Pfam_box | Symbol = Omega conotoxin | Name = | image =Ziconotide 1DW5.png | width = | caption =Schematic diagram of the three-dimensional [[protein structure|structure]] of ω-conotoxin MVIIA ([[ziconotide]]). [[Disulfide bond]]s are shown in gold. From {{PDB|1DW5}}. | Pfam= PF02950 | InterPro= IPR004214 | SMART= | Prosite = | SCOP = 2cco | TCDB = | OPM family= 120 | OPM protein= 1fyg | PDB= {{PDB3|1qfb}}A:55-62 {{PDB3|1dg0}}A:56-61 {{PDB3|1dfz}}A:55-61 {{PDB3|1dfy}}A:55-61 {{PDB3|1fyg}}A:46-70 {{PDB3|1mvj}} :46-71 {{PDB3|1mvi}} :46-70 {{PDB3|1dw5}}A:46-70 {{PDB3|1ttk}}A:46-70 {{PDB3|1feo}}A:46-71 {{PDB3|1omg}} :46-70 {{PDB3|1dw4}}A:46-70 {{PDB3|1tt3}}A:46-70 {{PDB3|1ttl}}A:46-72 {{PDB3|2cco}} :46-72 {{PDB3|1omc}} :46-72 {{PDB3|1tr6}}A:46-72 {{PDB3|1av3}} :46-72 {{PDB3|1kcp}} :46-72 {{PDB3|1fu3}}A:52-78 {{PDB3|1rmk}}A:52-82 {{PDB3|1y29}}A:1-28 {{PDB3|1wct}} :51-60 {{PDB3|1tck}} :2-22 {{PDB3|1tch}} :2-22 {{PDB3|1tcg}} :2-22 {{PDB3|1tcj}} :2-22 {{PDB3|1r9i}}A:4-24 {{PDB3|1as5}} :3-26 {{PDB3|1jlo}}A:3-26 }} A '''conotoxin''' is one of a group of [[Neurotoxicity|neurotoxic]] [[peptide]]s isolated from the venom of the marine [[cone snail]], genus ''[[Conus]]''. Conotoxins, which are peptides consisting of 10 to 30 [[amino acid]] residues, typically have one or more [[disulfide bond]]s. Conotoxins have a variety of mechanisms of actions, most of which have not been determined. However it appears that many of these peptides modulate the activity of [[ion channel]]s.<ref name="pmid14715910">{{cite journal | author = Terlau H, Olivera BM | title = Conus venoms: a rich source of novel ion channel-targeted peptides | journal = Physiol. Rev. | volume = 84 | issue = 1 | pages = 41–68 | year = 2004 | pmid = 14715910 | doi = 10.1152/physrev.00020.2003 | issn = }}</ref> ==Types and biological activities of conotoxins== The number of conotoxins whose activities have been determined so far is five, and they are called the α(alpha)-, δ(delta)-, κ(kappa)-, μ(mu)-, and ω(omega)- types. Each of the five types of conotoxins attacks a different target: * α-conotoxin inhibits [[acetylcholine receptor]]s at [[nerve]]s and [[muscle]]s.<ref name="pmid15182346">{{cite journal | author = Nicke A, Wonnacott S, Lewis RJ | title = Alpha-conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes | journal = Eur. J. Biochem. | volume = 271 | issue = 12 | pages = 2305–19 | year = 2004 | pmid = 15182346 | doi = 10.1111/j.1432-1033.2004.04145.x | issn = }}</ref> * δ-conotoxin inhibits the inactivation of [[voltage-dependent sodium channels]].<ref name="pmid15990094">{{cite journal | author = Leipold E, Hansel A, Olivera BM, Terlau H, Heinemann SH | title = Molecular interaction of delta-conotoxins with voltage-gated sodium channels | journal = FEBS Lett. | volume = 579 | issue = 18 | pages = 3881–4 | year = 2005 | pmid = 15990094 | doi = 10.1016/j.febslet.2005.05.077 | issn = }}</ref> * κ-conotoxin inhibits [[potassium channel]]s.<ref name="pmid9417043">{{cite journal | author = Shon KJ, Stocker M, Terlau H, Stühmer W, Jacobsen R, Walker C, Grilley M, Watkins M, Hillyard DR, Gray WR, Olivera BM | title = kappa-Conotoxin PVIIA is a peptide inhibiting the shaker K+ channel | journal = J. Biol. Chem. | volume = 273 | issue = 1 | pages = 33–8 | year = 1998 | pmid = 9417043 | doi = 10.1074/jbc.273.1.33 | issn = }}</ref> * μ-conotoxin inhibits voltage-dependent [[sodium channel]]s in muscles.<ref name="pmid15246758">{{cite journal | author = Li RA, Tomaselli GF | title = Using the deadly mu-conotoxins as probes of voltage-gated sodium channels | journal = Toxicon | volume = 44 | issue = 2 | pages = 117–22 | year = 2004 | pmid = 15246758 | doi = 10.1016/j.toxicon.2004.03.028 | issn = }}</ref> * ω-conotoxin inhibits N-type [[voltage-dependent calcium channel]]s.<ref name="pmid10822250">{{cite journal | author = Nielsen KJ, Schroeder T, Lewis R | title = Structure-activity relationships of omega-conotoxins at N-type voltage-sensitive calcium channels | journal = J. Mol. Recognit. | volume = 13 | issue = 2 | pages = 55–70 | year = 2000 | pmid = 10822250 | doi = 10.1002/(SICI)1099-1352(200003/04)13:2<55::AID-JMR488>3.0.CO;2-O| issn = | url = http://www3.interscience.wiley.com/cgi-bin/abstract/72502378/ABSTRACT | format = abstract}}</ref> Because N-type voltage-dependent calcium channels are related to [[algesia]] (sensitivity to [[pain]]) in the nervous system, ω-conotoxin has an [[analgesic]] effect: the effect of ω-conotoxin M VII A is 100 to 1000 times that of [[morphine]].<ref name="pmid9792182">{{cite journal | author = Bowersox SS, Luther R | title = Pharmacotherapeutic potential of omega-conotoxin MVIIA (SNX-111), an N-type neuronal calcium channel blocker found in the venom of Conus magus | journal = Toxicon | volume = 36 | issue = 11 | pages = 1651–8 | year = 1998 | pmid = 9792182 | doi = 10.1016/S0041-0101(98)00158-5 | issn = }}</ref> Therefore a synthetic version of ω-conotoxin M VII A has found application as an analgesic drug [[ziconotide]] (Prialt).<ref name="pmid16845440">{{cite journal | author = Prommer E | title = Ziconotide: a new option for refractory pain | journal = Drugs Today | volume = 42 | issue = 6 | pages = 369–78 | year = 2006 | pmid = 16845440 | doi = 10.1358/dot.2006.42.6.973534 | issn = }}</ref> ==Disulfide connectivities== Types of conotoxins also differ in the number and pattern of disulfide bonds.<ref name="PUB00016617">{{cite journal |author=Jones RM, McIntosh JM |title=Cone venom--from accidental stings to deliberate injection |journal=Toxicon |volume=39 |issue=10 |pages=1447–1451 |year=2001 |pmid=11478951 |doi=10.1016/S0041-0101(01)00145-3}}</ref> The disulfide bonding network, as well as specific amino acids in inter-cysteine loops, provide the specificity of conotoxins.<ref name="PUB00016622">{{cite journal |author=Sato K, Kini RM, Gopalakrishnakone P, Balaji RA, Ohtake A, Seow KT, Bay BH |title=lambda-conotoxins, a new family of conotoxins with unique disulfide pattern and protein folding. Isolation and characterization from the venom of Conus marmoreus |journal=J. Biol. Chem. |volume=275 |issue=50 |pages=39516–39522 |year=2000 |pmid=10988292 |doi=10.1074/jbc.M006354200}}</ref> ===Omega, delta and kappa conotoxins=== Omega, delta and kappa families of conotoxins have a knottin or inhibitor cysteine knot scaffold. The knottin scaffold is a very special disulfide-through-disulfide knot, in which the III-VI disulfide bond crosses the macrocycle formed by two other disulfide bonds (I-IV and II-V) and the interconnecting backbone segments, where I-VI indicates the six cysteine residues starting from the N-terminus. The cysteine arrangements are the same for omega, delta and kappa families, even though omega conotoxins are calcium channel blockers, whereas delta conotoxins delay the inactivation of sodium channels, and kappa conotoxins are potassium channel blockers.<ref name="PUB00016617" /> ===Mu conotoxins=== Mu conotoxins have two types of cysteine arrangements, but the knottin scaffold is not observed. Mu conotoxins target the voltage-gated sodium channels,<ref name="PUB00016617">{{cite journal |author=Jones RM, McIntosh JM |title=Cone venom--from accidental stings to deliberate injection |journal=Toxicon |volume=39 |issue=10 |pages=1447–1451 |year=2001 |pmid=11478951 |doi=10.1016/S0041-0101(01)00145-3}}</ref> and are useful probes for investigating voltage-dependent sodium channels of excitable tissues.<ref name="PUB00017021">{{cite journal |author=Zeikus RD, Gray WR, Cruz LJ, Olivera BM, Kerr L, Moczydlowski E, Yoshikami D |title=Conus geographus toxins that discriminate between neuronal and muscle sodium channels |journal=J. Biol. Chem. |volume=260 |issue=16 |pages=9280–9288 |year=1985 |pmid=2410412}}</ref> ===Alpha conotoxins=== Alpha conotoxins have two types of cysteine arrangements,<ref name="PUB00017022">{{cite journal |author=Gray WR, Olivera BM, Zafaralla GC, Ramilo CA, Yoshikami D, Nadasdi L, Hammerland LG, Kristipati R, Ramachandran J, Miljanich G |title=Novel alpha- and omega-conotoxins from Conus striatus venom |journal=Biochemistry |volume=31 |issue=41 |pages=9919–9926 |year=1992 |pmid=1390774 |doi=10.1021/bi00162a027}}</ref> and are competitive nicotinic acetylcholine receptor antagonists. == See also == * [[Contryphan]] ==References== {{Reflist|2}} ==External links== * {{cite web | url = http://www.expasy.org/cgi-bin/nicedoc.pl?PDOC60004 | title = PDOC60004: Conotoxin families signatures | author = Ramakumar S | authorlink = | coauthors = | date = 2006-10-01 | format = | work = [[PROSITE]] | publisher = Swiss Institute of Bioinformatics (SIB) | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 2008-06-27}} * {{MeshName|Conotoxins}} {{Protein tertiary structure}} {{InterPro content|IPR004214}} [[Category:Neurotoxins]] [[Category:Peripheral membrane proteins]] [[de:Conotoxine]] [[ja:コノトキシン]] [[pt:Conotoxina]]