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Conotoxin

 

 
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Conotoxin
 
 
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A conotoxin is one of a group of neurotoxic
Neurotoxicity

Neurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue....
 peptide
Peptide

Peptides are short polymers formed from the linking, in a defined order, of a-amino acids. The link between one amino acid residue and the next is known as an amide chemical bond or a peptide bond....
s isolated from the venom of the marine cone snail
Cone snail

The cone snails or cone shells, sometimes simply known as "cones", , are a taxonomic family of approximately 500 medium-sized to large, sophisticated predatory sea snails, marine gastropod mollusks....
, genus Conus
Conus

Conus is a genus of medium-sized to large, sophisticated predatory sea snails, marine gastropod molluscs, with the common names of cone snails, cone shells or cones....
.

Conotoxins, which are peptides consisting of 10 to 30 amino acid
Amino acid

In chemistry, an amino acid is a molecule containing both amine and carboxyl functional groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H2NCHRCOOH, where R is an organic substituent....
 residues, typically have one or more disulfide bond
Disulfide bond

In chemistry, a disulfide bond is a single covalent bond derived from the coupling of thiol groups. The linkage is also called an SS-bond or disulfide bridge....
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
Ion channel

Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of all living cell s by allowing the flow of ions down their electrochemical gradient....
s.

number of conotoxins whose activities have been determined so far is five, and they are called the a(alpha)-, d(delta)-, ?(kappa)-, µ(mu)-, and ?(omega)- types.






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Encyclopedia


A conotoxin is one of a group of neurotoxic
Neurotoxicity

Neurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue....
 peptide
Peptide

Peptides are short polymers formed from the linking, in a defined order, of a-amino acids. The link between one amino acid residue and the next is known as an amide chemical bond or a peptide bond....
s isolated from the venom of the marine cone snail
Cone snail

The cone snails or cone shells, sometimes simply known as "cones", , are a taxonomic family of approximately 500 medium-sized to large, sophisticated predatory sea snails, marine gastropod mollusks....
, genus Conus
Conus

Conus is a genus of medium-sized to large, sophisticated predatory sea snails, marine gastropod molluscs, with the common names of cone snails, cone shells or cones....
.

Conotoxins, which are peptides consisting of 10 to 30 amino acid
Amino acid

In chemistry, an amino acid is a molecule containing both amine and carboxyl functional groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H2NCHRCOOH, where R is an organic substituent....
 residues, typically have one or more disulfide bond
Disulfide bond

In chemistry, a disulfide bond is a single covalent bond derived from the coupling of thiol groups. The linkage is also called an SS-bond or disulfide bridge....
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
Ion channel

Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of all living cell s by allowing the flow of ions down their electrochemical gradient....
s.

Types and biological activities of conotoxins

The number of conotoxins whose activities have been determined so far is five, and they are called the a(alpha)-, d(delta)-, ?(kappa)-, µ(mu)-, and ?(omega)- types. Each of the five types of conotoxins attacks a different target:

  • a-conotoxin inhibits nicotinic acetylcholine receptor
    Acetylcholine receptor

    An acetylcholine receptor is an integral membrane protein that responds to the binding of the neurotransmitter acetylcholine....
    s at nerve
    Nerve

    A nerve is an enclosed, cable-like bundle of Peripheral nervous system axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons....
    s and muscle
    MUSCLE

    MUSCLE is public domain, multiple sequence alignment software for protein and nucleotide sequences.MUSCLE is integrated into UGENE bioinformatics tool as a plugin....
    s.
  • d-conotoxin inhibits the inactivation of voltage-dependent sodium channels.
  • ?-conotoxin inhibits potassium channel
    Potassium channel

    In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms....
    s.
  • µ-conotoxin inhibits voltage-dependent sodium channels in muscles.
  • ?-conotoxin inhibits N-type voltage-dependent calcium channel
    Voltage-dependent calcium channel

    Voltage-dependent calcium channels are a group of voltage-gated ion channel ion channels found in excitable cells with a Permeability to the ion calcium....
    s. Because N-type voltage-dependent calcium channels are related to algesia
    Algesia

    Algesia, from the Greek language word algesis, is the sensitivity to Pain and nociception. The term is sometimes used to refer to hyperalgesia ....
     (sensitivity to pain
    Pain

    Pain, in the sense of physical pain, is a typical sensory experience that may be described as the unpleasant awareness of a noxious stimulus or bodily harm....
    ) in the nervous system, ?-conotoxin has an analgesic
    Analgesic

    An analgesic is any member of the diverse group of Medication used to relieve pain . The word analgesic derives from Greek an- and algos ....
     effect: the effect of ?-conotoxin M VII A is 100 to 1000 times that of morphine
    Morphine

    Morphine is a highly potent opiate analgesic Medication, is the principal active agent in opium, and is considered to be the prototypical opioid....
    . Therefore a synthetic version of ?-conotoxin M VII A has found application as an analgesic drug ziconotide
    Ziconotide

    Ziconotide is a non-Opium, non-NSAID, non-local Anaesthetic drugs used for the amelioration of chronic pain. Derived from the cone snail Conus magus, it is the synthesis of the cone snail peptide ?-conotoxin M-VII-A, an N-type calcium channel blocker....
     (Prialt).


Disulfide connectivities

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

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.

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, and are useful probes for investigating voltage-dependent sodium channels of excitable tissues.

Alpha conotoxins

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

See also

  • Contryphan
    Contryphan

    The contryphans are a family of peptides which are active constituents of the poisonous venom produced by cone snail . The two amino acid cysteine residues in contryphans are linked by a disulfide bond....


External links

  • on-line lecture by Baldomero Olivera
    Baldomero Olivera

    Baldomero Olivera is a Philippine chemist most famous for discovery of many cone snail toxins important for neuroscience. These molecules, called conotoxins led to a breakthrough in the study of ion channels and neuro-muscular synapses....