请输入您要查询的百科知识：

　

词条 Conotoxin
释义

  1. Hypervariability

  2. Disulfide connectivities

  3. Types and biological activities

     Alpha  Delta and kappa, and omega   Mu 

  4. See also

  5. References

  6. External links

{{Pfam_box
| Symbol = Toxin_8
| Name = Alpha conotoxin precursor
| 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 = PDOC60004
| SCOP = 1mii
| TCDB =
| OPM family = 148
| OPM protein = 1akg
| PDB =
}}{{Pfam_box
| Symbol = Conotoxin
| Name = Omega conotoxin
| image =Ziconotide 1DW5.png
| width =
| caption =Schematic diagram of the three-dimensional structure of ω-conotoxin MVIIA (ziconotide). Disulfide bonds are shown in gold. From {{PDB|1DW5}}.
| Pfam= PF02950
| InterPro= IPR004214
| SMART=
| PROSITE =
| SCOP = 2cco
| TCDB =
| OPM family= 112
| OPM protein= 1fyg
| PDB=
}}

A conotoxin is one of a group of neurotoxic peptides 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 bonds. 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 channels.[1]

Over the last few decades conotoxins have been the subject of pharmacological interest.[2]

The LD50 of conotoxin is 50 ng/kg.[3]{{failed_verification|date=April 2017}}

Hypervariability

Conotoxins are hypervariable even within the same species. They do not act within a body where they are produced (endogenously) but act on other organisms.[4] Therefore, conotoxins genes experience less selection against mutations (like gene duplication and nonsynonymous substitution), and mutations remain in the genome longer, allowing more time for potentially beneficial novel functions to arise.[5] Variability in conotoxin components reduces the likelihood that prey organisms will develop resistance; thus cone snails are under constant selective pressure to maintain polymorphism in these genes because failing to evolve and adapt will lead to extinction (Red Queen hypothesis).[6]

Disulfide connectivities

Types of conotoxins also differ in the number and pattern of disulfide bonds.[7] The disulfide bonding network, as well as specific amino acids in inter-cysteine loops, provide the specificity of conotoxins.[8]

Types and biological activities

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 nicotinic acetylcholine receptors at nerves and muscles.[9]
  • δ-conotoxin inhibits fast inactivation of voltage-dependent sodium channels.[10]
  • κ-conotoxin inhibits potassium channels.[11]
  • μ-conotoxin inhibits voltage-dependent sodium channels in muscles.[12]
  • ω-conotoxin inhibits N-type voltage-dependent calcium channels.[13] 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.[14] Therefore, a synthetic version of ω-conotoxin M VII A has found application as an analgesic drug ziconotide (Prialt).[15]

Alpha

Alpha conotoxins have two types of cysteine arrangements,[16] and are competitive nicotinic acetylcholine receptor antagonists.

Delta and kappa, and omega

Omega, delta and kappa families of conotoxins have a knottin or inhibitor cystine 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.[7]

Mu

{{Infobox protein family
| Symbol = Mu-conotoxin
| Name = Mu-conotoxin
| image = PDB 1r9i EBI.jpg
| width =
| caption = nmr solution structure of piiia toxin, nmr, 20 structures
| Pfam = PF05374
| Pfam_clan = CL0083
| InterPro = IPR008036
| SMART =
| PROSITE =
| MEROPS =
| SCOP = 1gib
| TCDB =
| OPM family = 112
| OPM protein = 1ag7
| CAZy =
| CDD =
}}

Mu-conotoxins have two types of cysteine arrangements, but the knottin scaffold is not observed.[17] Mu-conotoxins target the muscle-specific voltage-gated sodium channels,[7] and are useful probes for investigating voltage-dependent sodium channels of excitable tissues.[17][18] Mu-conotoxins target the voltage-gated sodium channels, preferentially those of skeletal muscle,[19] and are useful probes for investigating voltage-dependent sodium channels of excitable tissues.[20]

Different subtypes of voltage-gated sodium channels are found in different tissues in mammals, e.g., in muscle and brain, and studies have been carried out to determine the sensitivity and specificity of the mu-conotoxins for the different isoforms.[21]

See also

  • Contryphan
  • Conantokins

References

{{InterPro content|IPR004214|IPR008036}}
1. ^{{cite journal | vauthors = 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 }}
2. ^{{cite journal| vauthors=Olivera BM, Teichert RW| title=Diversity of the neurotoxic Conus peptides: a model for concerted pharmacological discovery. | journal=Mol Interv | year= 2007 | volume= 7 | issue= 5 | pages= 251–60 | pmid=17932414 | doi=10.1124/mi.7.5.7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17932414 }}
3. ^{{cite web |url=http://www.aristatek.com/Newsletter/MAY08/TechSpeak.pdf |title=Archived copy |accessdate=2017-03-31 |deadurl=no |archiveurl=https://web.archive.org/web/20170829050422/http://www.aristatek.com/Newsletter/MAY08/TechSpeak.pdf |archivedate=2017-08-29 |df= }}
4. ^{{cite journal | vauthors = Olivera BM, Watkins M, Bandyopadhyay P, Imperial JS, de la Cotera EP, Aguilar MB, Vera EL, Concepcion GP, Lluisma A | title = Adaptive radiation of venomous marine snail lineages and the accelerated evolution of venom peptide genes | journal = Ann. N. Y. Acad. Sci. | volume = 1267 | issue = 1| pages = 61–70 |date=September 2012 | pmid = 22954218 | pmc = 3488454 | doi = 10.1111/j.1749-6632.2012.06603.x }}
5. ^{{cite journal | vauthors = Wong ES, Belov K | title = Venom evolution through gene duplications | journal = Gene | volume = 496 | issue = 1 | pages = 1–7 |date=March 2012 | pmid = 22285376 | doi = 10.1016/j.gene.2012.01.009 }}
6. ^{{cite journal | vauthors = Liow LH, Van Valen L, Stenseth NC | title = Red Queen: from populations to taxa and communities | journal = Trends Ecol. Evol. | volume = 26 | issue = 7 | pages = 349–58 |date=July 2011 | pmid = 21511358 | doi = 10.1016/j.tree.2011.03.016 }}
7. ^1 2 {{cite journal |vauthors=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}}
8. ^{{cite journal |vauthors=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}}
9. ^{{cite journal | vauthors = 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 = 2305–2319 | year = 2004 | pmid = 15182346 | doi = 10.1111/j.1432-1033.2004.04145.x }}
10. ^{{cite journal | vauthors = 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 = 3881–3884 | year = 2005 | pmid = 15990094 | doi = 10.1016/j.febslet.2005.05.077 }}
11. ^{{cite journal | vauthors = 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 = 33–38 | year = 1998 | pmid = 9417043 | doi = 10.1074/jbc.273.1.33 }}
12. ^{{cite journal | vauthors = Li RA, Tomaselli GF | title = Using the deadly mu-conotoxins as probes of voltage-gated sodium channels | journal = Toxicon | volume = 44 | issue = 2 | pages = 117–122 | year = 2004 | pmid = 15246758 | doi = 10.1016/j.toxicon.2004.03.028 | pmc = 2698010 }}
13. ^{{cite journal | vauthors = 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| url = http://www3.interscience.wiley.com/cgi-bin/abstract/72502378/ABSTRACT | archive-url = https://archive.today/20110813050839/http://www3.interscience.wiley.com/cgi-bin/abstract/72502378/ABSTRACT | dead-url = yes | archive-date = 2011-08-13 | format = abstract}}
14. ^{{cite journal | vauthors = 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 = 1651–1658 | year = 1998 | pmid = 9792182 | doi = 10.1016/S0041-0101(98)00158-5 }}
15. ^{{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 }}
16. ^{{cite journal |vauthors=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=11864–11873 |year=1992 |pmid=1390774 |doi=10.1021/bi00162a027}}
17. ^1 {{cite journal | vauthors = Nielsen KJ, Watson M, Adams DJ, Hammarström AK, Gage PW, Hill JM, Craik DJ, Thomas L, Adams D, Alewood PF, Lewis RJ | title= Solution structure of mu-conotoxin PIIIA, a preferential inhibitor of persistent tetrodotoxin-sensitive sodium channels| journal = J. Biol. Chem. | volume = 277 | issue = 30 | pages = 27247–55 |date=July 2002 | pmid = 12006587 | doi = 10.1074/jbc.M201611200 | url = https://researchonline.jcu.edu.au/266/1/thomas_1.pdf}}
18. ^{{cite journal |vauthors=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=9280–8 |year=1985 |pmid=2410412}}
19. ^{{cite journal | vauthors = McIntosh JM, Jones RM | title = Cone venom--from accidental stings to deliberate injection | journal = Toxicon | volume = 39 | issue = 10 | pages = 1447–51 |date=October 2001 | pmid = 11478951 | doi = 10.1016/S0041-0101(01)00145-3| url = }}
20. ^{{cite journal | vauthors = Cruz LJ, Gray WR, Olivera BM, Zeikus RD, Kerr L, Yoshikami D, Moczydlowski E | title = Conus geographus toxins that discriminate between neuronal and muscle sodium channels | journal = J. Biol. Chem. | volume = 260 | issue = 16 | pages = 9280–8 |date=August 1985 | pmid = 2410412 | doi = | url = }}
21. ^{{cite journal| author=Floresca CZ| title=A comparison of the mu-conotoxins by [3H]saxitoxin binding assays in neuronal and skeletal muscle sodium channel. | journal=Toxicol Appl Pharmacol | year= 2003 | volume= 190 | issue= 2 | pages= 95–101 | pmid=12878039 | doi= 10.1016/s0041-008x(03)00153-4| pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12878039 }}

External links

  • {{MeshName|Conotoxins}}
  • {{cite web|url=https://www.ibiology.org/archive/conus-peptides/|title=Conus Peptides|author=Baldomero "Toto" Olivera's Short Talk|first=|date=|website=|access-date=}}
  • {{cite web | url = http://www.conoserver.org/ | title = ConoServer | vauthors = Kaas Q, Westermann JC, Halai R, Wang CK, Craik DJ | date = | format = | work = | publisher = Institute of Molecular Bioscience, The University of Queensland, Australia| pages = | language = | quote = A database for conopeptide sequences and structures| accessdate = 2009-06-02}}
{{Protein tertiary structure}}{{Toxins}}{{Ion channel modulators}}{{Nicotinic acetylcholine receptor modulators}}

5 : Invertebrate toxins|Ion channel toxins|Neurotoxins|Nicotinic antagonists|Peripheral membrane proteins
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/9/23 3:32:12