Summary: Conotoxin
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This is the Wikipedia entry entitled "Conotoxin". More...
Conotoxin Edit Wikipedia article
| Alpha conotoxin precursor | |||||||||
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 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. |
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| Identifiers | |||||||||
| Symbol | Toxin_8 | ||||||||
| Pfam | PF07365 | ||||||||
| InterPro | IPR009958 | ||||||||
| PROSITE | PDOC60004 | ||||||||
| SCOP | 1mii | ||||||||
| SUPERFAMILY | 1mii | ||||||||
| OPM superfamily | 157 | ||||||||
| OPM protein | 1akg | ||||||||
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| Omega conotoxin | |||||||||
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 Schematic diagram of the three-dimensional structure of ω-conotoxin MVIIA (ziconotide). Disulfide bonds are shown in gold. From PDB 1DW5. |
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| Identifiers | |||||||||
| Symbol | Conotoxin | ||||||||
| Pfam | PF02950 | ||||||||
| InterPro | IPR004214 | ||||||||
| SCOP | 2cco | ||||||||
| SUPERFAMILY | 2cco | ||||||||
| OPM superfamily | 120 | ||||||||
| OPM protein | 1fyg | ||||||||
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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 subject of pharmacological interest.[2]
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[edit] 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 nicotinic acetylcholine receptors at nerves and muscles.[3]
- δ-conotoxin inhibits the inactivation of voltage-dependent sodium channels.[4]
- κ-conotoxin inhibits potassium channels.[5]
- μ-conotoxin inhibits voltage-dependent sodium channels in muscles.[6]
- ω-conotoxin inhibits N-type voltage-dependent calcium channels.[7] 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.[8] Therefore a synthetic version of ω-conotoxin M VII A has found application as an analgesic drug ziconotide (Prialt).[9]
[edit] Disulfide connectivities
Types of conotoxins also differ in the number and pattern of disulfide bonds.[10] The disulfide bonding network, as well as specific amino acids in inter-cysteine loops, provide the specificity of conotoxins.[11]
[edit] 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.[10]
[edit] Mu conotoxins
| Mu-conotoxin | |||||||||
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 nmr solution structure of piiia toxin, nmr, 20 structures |
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| Identifiers | |||||||||
| Symbol | Mu-conotoxin | ||||||||
| Pfam | PF05374 | ||||||||
| Pfam clan | CL0083 | ||||||||
| InterPro | IPR008036 | ||||||||
| SCOP | 1gib | ||||||||
| SUPERFAMILY | 1gib | ||||||||
| OPM superfamily | 120 | ||||||||
| OPM protein | 1ag7 | ||||||||
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Mu-conotoxins have two types of cysteine arrangements, but the knottin scaffold is not observed.[12] Mu-conotoxins target the muscle-specific voltage-gated sodium channels,[10] and are useful probes for investigating voltage-dependent sodium channels of excitable tissues.[12][13] Mu-conotoxins target the voltage-gated sodium channels, preferentially those of skeletal muscle,[14] and are useful probes for investigating voltage-dependent sodium channels of excitable tissues.[15]
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.[16]
[edit] Alpha conotoxins
Alpha conotoxins have two types of cysteine arrangements,[17] and are competitive nicotinic acetylcholine receptor antagonists.
[edit] See also
[edit] References
- ^ Terlau H, Olivera BM (2004). "Conus venoms: a rich source of novel ion channel-targeted peptides". Physiol. Rev. 84 (1): 41–68. doi:10.1152/physrev.00020.2003. PMID 14715910.
- ^ Olivera BM, Teichert RW (2007). "Diversity of the neurotoxic Conus peptides: a model for concerted pharmacological discovery.". Mol Interv 7 (5): 251–60. doi:10.1124/mi.7.5.7. PMID 17932414.
- ^ Nicke A, Wonnacott S, Lewis RJ (2004). "Alpha-conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes". Eur. J. Biochem. 271 (12): 2305–2319. doi:10.1111/j.1432-1033.2004.04145.x. PMID 15182346.
- ^ Leipold E, Hansel A, Olivera BM, Terlau H, Heinemann SH (2005). "Molecular interaction of delta-conotoxins with voltage-gated sodium channels". FEBS Lett. 579 (18): 3881–3884. doi:10.1016/j.febslet.2005.05.077. PMID 15990094.
- ^ Shon KJ, Stocker M, Terlau H, Stühmer W, Jacobsen R, Walker C, Grilley M, Watkins M, Hillyard DR, Gray WR, Olivera BM (1998). "kappa-Conotoxin PVIIA is a peptide inhibiting the shaker K+ channel". J. Biol. Chem. 273 (1): 33–38. doi:10.1074/jbc.273.1.33. PMID 9417043.
- ^ Li RA, Tomaselli GF (2004). "Using the deadly mu-conotoxins as probes of voltage-gated sodium channels". Toxicon 44 (2): 117–122. doi:10.1016/j.toxicon.2004.03.028. PMC 2698010. PMID 15246758.
- ^ Nielsen KJ, Schroeder T, Lewis R (2000). "Structure-activity relationships of omega-conotoxins at N-type voltage-sensitive calcium channels" (abstract). J. Mol. Recognit. 13 (2): 55–70. doi:10.1002/(SICI)1099-1352(200003/04)13:2<55::AID-JMR488>3.0.CO;2-O. PMID 10822250.
- ^ Bowersox SS, Luther R (1998). "Pharmacotherapeutic potential of omega-conotoxin MVIIA (SNX-111), an N-type neuronal calcium channel blocker found in the venom of Conus magus". Toxicon 36 (11): 1651–1658. doi:10.1016/S0041-0101(98)00158-5. PMID 9792182.
- ^ Prommer E (2006). "Ziconotide: a new option for refractory pain". Drugs Today 42 (6): 369–78. doi:10.1358/dot.2006.42.6.973534. PMID 16845440.
- ^ a b c Jones RM, McIntosh JM (2001). "Cone venom--from accidental stings to deliberate injection". Toxicon 39 (10): 1447–1451. doi:10.1016/S0041-0101(01)00145-3. PMID 11478951.
- ^ Sato K, Kini RM, Gopalakrishnakone P, Balaji RA, Ohtake A, Seow KT, Bay BH (2000). "lambda-conotoxins, a new family of conotoxins with unique disulfide pattern and protein folding. Isolation and characterization from the venom of Conus marmoreus". J. Biol. Chem. 275 (50): 39516–39522. doi:10.1074/jbc.M006354200. PMID 10988292.
- ^ a b Nielsen KJ, Watson M, Adams DJ, Hammarström AK, Gage PW, Hill JM, Craik DJ, Thomas L, Adams D, Alewood PF, Lewis RJ (July 2002). J. Biol. Chem. 277 (30): 27247–55. doi:10.1074/jbc.M201611200. PMID 12006587.
- ^ Zeikus RD, Gray WR, Cruz LJ, Olivera BM, Kerr L, Moczydlowski E, Yoshikami D (1985). "Conus geographus toxins that discriminate between neuronal and muscle sodium channels". J. Biol. Chem. 260 (16): 9280–8. PMID 2410412.
- ^ McIntosh JM, Jones RM (October 2001). "Cone venom--from accidental stings to deliberate injection". Toxicon 39 (10): 1447–51. doi:10.1016/S0041-0101(01)00145-3. PMID 11478951.
- ^ Cruz LJ, Gray WR, Olivera BM, Zeikus RD, Kerr L, Yoshikami D, Moczydlowski E (August 1985). "Conus geographus toxins that discriminate between neuronal and muscle sodium channels". J. Biol. Chem. 260 (16): 9280–8. PMID 2410412.
- ^ Floresca CZ (2003). "A comparison of the mu-conotoxins by [3H]saxitoxin binding assays in neuronal and skeletal muscle sodium channel.". Toxicol Appl Pharmacol 190 (2): 95–101. PMID 12878039.
- ^ Gray WR, Olivera BM, Zafaralla GC, Ramilo CA, Yoshikami D, Nadasdi L, Hammerland LG, Kristipati R, Ramachandran J, Miljanich G (1992). "Novel alpha- and omega-conotoxins from Conus striatus venom". Biochemistry 31 (41): 11864–11873. doi:10.1021/bi00162a027. PMID 1390774.
This article incorporates text from the public domain Pfam and InterPro IPR008036
[edit] External links
- Conotoxins at the US National Library of Medicine Medical Subject Headings (MeSH)
- Baldomero "Toto" Olivera. "iBioSeminar on Conus Peptides". The American Society for Cell Biology.
- Kaas Q, Westermann JC, Halai R, Wang CK, Craik DJ. "ConoServer". Institute of Molecular Bioscience, The University of Queensland, Australia. Retrieved 2009-06-02. "A database for conopeptide sequences and structures"
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This article incorporates text from the public domain Pfam and InterPro IPR004214
This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
This is the Wikipedia entry entitled "Contryphan". More...
Contryphan Edit Wikipedia article
| Contryphan | |||||||||
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| NMR structure of Contryphan-Vn. The peptide backbone is depicted by a curved tube while the amino acid side-chains are represented by capped sticks. Carbon atoms are colored grey, nitrogen atoms blue, oxygen atoms red, and sulfur atoms yellow.[1] . |
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| Identifiers | |||||||||
| Symbol | Contryphan_CS | ||||||||
| Pfam | PF02950 | ||||||||
| InterPro | IPR011062 | ||||||||
| PROSITE | PS60027 | ||||||||
| SCOP | 2cco | ||||||||
| SUPERFAMILY | 2cco | ||||||||
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The contryphans (conus + tryptophan) are a family of peptides that are active constituents of the poisonous venom produced by cone snail (genus conus). The two amino acid cysteine residues in contryphans are linked by a disulfide bond. In addition, contryphans undergo an unusual degree of post-translational modification including epimerization of leucine and tryptophan, tryptophan bromination, amidation of the C-terminus, and proline hydroxylation.[2]
Contents |
[edit] Family members
Contryphan family members include:
| Peptide | Sequence | Species | Reference |
|---|---|---|---|
| Des(Gly1)contryphan-R | COwEPWC-NH2 | C. radiatus | [3] |
| Contryphan-R | GCOwEPWC-NH2 | C. radiatus | [3] |
| Bromocontyphan-R | GCOwEPXC-NH2 | C. radiatus | [4] |
| Contryphan-Sm | GCOwQPWC-NH2 | C. stercusmuscarum | [5] |
| Contryphan-P | GCOwDPWC-NH2 | C. purpurascens | [5] |
| Contryphan-R/Tx | GCOwEPWC-NH2 | C. textile | [5] |
| Contryphan-Tx | GCOWQPYC-NH2 | C. textile | [5] |
| Contryphan-Vn | GDCPwKPWC-NH2 | C. ventricosus | [6] |
| Leu-contryphan-P | GCVlLPWC-OH | C. purpurascens | [7] |
| Leu-contryphan-Tx | CVlYPWC-NH2 | C. textile | [5] |
| Glaconryphan-M | NγSγCPWHPWC-NH2 | C. marmoreus | [2] |
where the sequence abbreviations stand for:
- O = 4-trans-hydroxyproline,
- l = D-leucine, L = L-leucine,
- w = D-tryptophan, W = L-tryptophan,
- γ = gamma-carboxyglutamic acid,
- NH2 = C-terminal amidation
and the remainder of the letters refer to the standard one letter abbreviations for amino acids.
[edit] Mechanism of toxicity
The venom of cone snails cause paralysis of their fish prey. The molecular target has not been determined for all contryphan peptides, however it is known that contryphan-Vn is a Ca2+-dependent K+ channel modulator,[6] while glacontryphan-M is a L-type calcium channel blocker.[2]
[edit] See also
[edit] References
- ^ PDB 1NXN; Eliseo T, Cicero DO, Romeo C, Schininà ME, Massilia GR, Polticelli F, Ascenzi P, Paci M (June 2004). "Solution structure of the cyclic peptide contryphan-Vn, a Ca2+-dependent K+ channel modulator". Biopolymers 74 (3): 189–98. doi:10.1002/bip.20025. PMID 15150794.
- ^ a b c Hansson K, Ma X, Eliasson L, Czerwiec E, Furie B, Furie BC, Rorsman P, Stenflo J (2004). "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 (31): 32453–63. doi:10.1074/jbc.M313825200. PMID 15155730.
- ^ a b Jimenéz EC, Olivera BM, Gray WR, Cruz LJ (1996). "Contryphan is a D-tryptophan-containing Conus peptide". J. Biol. Chem. 271 (45): 28002–5. doi:10.1074/jbc.271.45.28002. PMID 8910408.
- ^ Jimenez EC, Craig AG, Watkins M, Hillyard DR, Gray WR, Gulyas J, Rivier JE, Cruz LJ, Olivera BM (1997). "Bromocontryphan: post-translational bromination of tryptophan". Biochemistry 36 (5): 989–94. doi:10.1021/bi962840p. PMID 9033387.
- ^ a b c d e Jacobsen R, Jimenez EC, Grilley M, Watkins M, Hillyard D, Cruz LJ, Olivera BM (1998). "The contryphans, a D-tryptophan-containing family of Conus peptides: interconversion between conformers". J. Pept. Res. 51 (3): 173–9. doi:10.1111/j.1399-3011.1998.tb01213.x. PMID 9531419.
- ^ a b Massilia GR, Schininà ME, Ascenzi P, Polticelli F (2001). "Contryphan-Vn: a novel peptide from the venom of the Mediterranean snail Conus ventricosus". Biochem. Biophys. Res. Commun. 288 (4): 908–13. doi:10.1006/bbrc.2001.5833. PMID 11688995.
- ^ Jacobsen RB, Jimenez EC, De la Cruz RG, Gray WR, Cruz LJ, Olivera BM (1999). "A novel D-leucine-containing Conus peptide: diverse conformational dynamics in the contryphan family". J. Pept. Res. 54 (2): 93–9. doi:10.1034/j.1399-3011.1999.00093.x. PMID 10461743.
[edit] External links
- Contryphan at the US National Library of Medicine Medical Subject Headings (MeSH)
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This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Conotoxin Provide feedback
Conotoxins are small snail toxins that block ion channels.
Literature references
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Gray WR, Olivera BM, Cruz LJ; , Annu Rev Biochem 1988;57:665-700.: Peptide toxins from venomous Conus snails. PUBMED:3052286 EPMC:3052286
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Pallaghy PK, Duggan BM, Pennington MW, Norton RS; , J Mol Biol 1993;234:405-420.: Three-dimensional structure in solution of the calcium channel blocker omega-conotoxin PUBMED:8230223 EPMC:8230223
Internal database links
| SCOOP: | GRP |
External database links
| PANDIT: | PF02950 |
| Pseudofam: | PF02950 |
| SCOP: | 2cco |
| SYSTERS: | Conotoxin |
This tab holds annotation information from the InterPro database.
InterPro entry IPR004214
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 [PUBMED:11478951]. 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.
The disulphide bonding network, as well as specific amino acids in inter-cysteine loops, provide the specificity of conotoxins [PUBMED:10988292]. 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 [PUBMED:11478951]. Mu conotoxins have two types of cysteine arrangements, but the knottin scaffold is not observed. Mu conotoxins target the voltage-gated sodium channels [PUBMED:11478951], and are useful probes for investigating voltage-dependent sodium channels of excitable tissues [PUBMED:2410412]. Alpha conotoxins have two types of cysteine arrangements [PUBMED:1390774], and are competitive nicotinic acetylcholine receptor antagonists.
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Cellular component | extracellular region (GO:0005576) |
| Molecular function | ion channel inhibitor activity (GO:0008200) |
| Biological process | pathogenesis (GO:0009405) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan Omega_toxin (CL0083), which contains the following 19 members:
Agouti Albumin_I Conotoxin Mu-conotoxin Omega-toxin Tachystatin_B Toxin_11 Toxin_12 Toxin_16 Toxin_18 Toxin_21 Toxin_22 Toxin_23 Toxin_24 Toxin_27 Toxin_30 Toxin_7 Toxin_9 UPF0506Alignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...
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| Seed (112) |
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| RP15 (0) |
RP35 (0) |
RP55 (1) |
RP75 (2) |
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| Seed (112) |
Full (926) |
Representative proteomes | NCBI (953) |
Meta (0) |
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| RP15 (0) |
RP35 (0) |
RP55 (1) |
RP75 (2) |
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
External links
MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Pfam-B_529 (release 6.4) |
| Previous IDs: | none |
| Type: | Domain |
| Author: | Bateman A |
| Number in seed: | 112 |
| Number in full: | 926 |
| Average length of the domain: | 70.10 aa |
| Average identity of full alignment: | 26 % |
| Average coverage of the sequence by the domain: | 96.65 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 75 | ||||||||||||
| Family (HMM) version: | 12 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Conotoxin domain has been found. There are 27 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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