Sandbox 174: Difference between revisions
Simon Loewen (talk | contribs) No edit summary |
Simon Loewen (talk | contribs) No edit summary |
||
| Line 1: | Line 1: | ||
{{STRUCTURE_2abx | PDB=2abx | SCENE= }} | |||
=Alpha-Bungarotoxin= | =Alpha-Bungarotoxin= | ||
Alpha-Bungarotoxin (α-BGT) is a nicotinic cholinergic antagonist that is found within the venom of ''Bungarus multicinctus'', a South-asian snake belonging to a group commonly known as kraits. Belonging to the Elapidae Family, which consist of cobras, kraits, tiger snakes, and mambas, the venom of ''Bungarus multicuntus'' is a complex mixture of many different molecules<ref name="main">Love, A.R (FINISH)</ref> α-BGT belongs to a family of homologous proteins that act as a neurotoxic agent in the venom of these snakes. α-BGT is known to bind irreversibly to the acetylcholine receptor found at the neuromuscular junction, causing respiratory failure, paralysis, and death, as well as play an antagonstic role in binding the α7 nicotinic acetylcholine receptor in the brain. | Alpha-Bungarotoxin (α-BGT) is a nicotinic cholinergic antagonist that is found within the venom of ''Bungarus multicinctus'', a South-asian snake belonging to a group commonly known as kraits. Belonging to the Elapidae Family, which consist of cobras, kraits, tiger snakes, and mambas, the venom of ''Bungarus multicuntus'' is a complex mixture of many different molecules<ref name="main">Love, A.R (FINISH)</ref> α-BGT belongs to a family of homologous proteins that act as a neurotoxic agent in the venom of these snakes. α-BGT is known to bind irreversibly to the acetylcholine receptor found at the neuromuscular junction, causing respiratory failure, paralysis, and death, as well as play an antagonstic role in binding the α7 nicotinic acetylcholine receptor in the brain. | ||
| Line 8: | Line 7: | ||
A large amount of highly homologous snake neurotoxins have been sequenced (>60), and can be grouped into two major classes. Short neurotoxins are between 60-62 amino acids long, and consist of four disulphide bonds, and long neurotoxins, which α-BGT falls under, are between 71-74 amino acids long and contain five <scene name='Sandbox_174/Disulphides/2'>Disulphide Bonds</scene>. α-BGT contains 74 amino acids, and is one of the major components of ''Bungarus multicuntus'' venom. Chemical modifications of individual residues has shown that no single amino acid is mandatory for binding, signifying the significance of structure, rather than sequence, and the concept of multicontact interaction with the acetylcholine receptor <ref> Karlsson, 1979;Low 1979</ref>. The importance of structure in binding has been tested by Love & Stroud (1986)<ref name="main">Love, A.R (FINISH)</ref> by determining whether the homology and common mode of action of neurotoxins is facilitated by the three-dimensional structure. Using X-ray crystallography at various resolutions, neurotoxins erabutoxin and cobratoxin were compared to that of α-BGT to determine the level of three-dimensional similarity. | A large amount of highly homologous snake neurotoxins have been sequenced (>60), and can be grouped into two major classes. Short neurotoxins are between 60-62 amino acids long, and consist of four disulphide bonds, and long neurotoxins, which α-BGT falls under, are between 71-74 amino acids long and contain five <scene name='Sandbox_174/Disulphides/2'>Disulphide Bonds</scene>. α-BGT contains 74 amino acids, and is one of the major components of ''Bungarus multicuntus'' venom. Chemical modifications of individual residues has shown that no single amino acid is mandatory for binding, signifying the significance of structure, rather than sequence, and the concept of multicontact interaction with the acetylcholine receptor <ref> Karlsson, 1979;Low 1979</ref>. The importance of structure in binding has been tested by Love & Stroud (1986)<ref name="main">Love, A.R (FINISH)</ref> by determining whether the homology and common mode of action of neurotoxins is facilitated by the three-dimensional structure. Using X-ray crystallography at various resolutions, neurotoxins erabutoxin and cobratoxin were compared to that of α-BGT to determine the level of three-dimensional similarity. | ||
<scene name='Sandbox_174/Domain B/1'>Domain B</scene> | |||
Domain B | |||
Revision as of 23:19, 25 March 2010
Alpha-BungarotoxinAlpha-Bungarotoxin
Alpha-Bungarotoxin (α-BGT) is a nicotinic cholinergic antagonist that is found within the venom of Bungarus multicinctus, a South-asian snake belonging to a group commonly known as kraits. Belonging to the Elapidae Family, which consist of cobras, kraits, tiger snakes, and mambas, the venom of Bungarus multicuntus is a complex mixture of many different molecules[1] α-BGT belongs to a family of homologous proteins that act as a neurotoxic agent in the venom of these snakes. α-BGT is known to bind irreversibly to the acetylcholine receptor found at the neuromuscular junction, causing respiratory failure, paralysis, and death, as well as play an antagonstic role in binding the α7 nicotinic acetylcholine receptor in the brain.
General StructureGeneral Structure
A large amount of highly homologous snake neurotoxins have been sequenced (>60), and can be grouped into two major classes. Short neurotoxins are between 60-62 amino acids long, and consist of four disulphide bonds, and long neurotoxins, which α-BGT falls under, are between 71-74 amino acids long and contain five . α-BGT contains 74 amino acids, and is one of the major components of Bungarus multicuntus venom. Chemical modifications of individual residues has shown that no single amino acid is mandatory for binding, signifying the significance of structure, rather than sequence, and the concept of multicontact interaction with the acetylcholine receptor [2]. The importance of structure in binding has been tested by Love & Stroud (1986)[1] by determining whether the homology and common mode of action of neurotoxins is facilitated by the three-dimensional structure. Using X-ray crystallography at various resolutions, neurotoxins erabutoxin and cobratoxin were compared to that of α-BGT to determine the level of three-dimensional similarity. Domain B
Active sites &Active sites &
FunctionsFunctions
Elapidae neurotoxins bind specifically and tightly (with a very high affinity) in a non-covalent manner to the nicotinic acetylcholine receptors in cholinergic synapses of their victims. This prevents normal neurotransmitter-induced channel opening, which in turn blocks postsynaptic membrane depolarization[1].
α7 nicotinic acetylcholine receptor bindingα7 nicotinic acetylcholine receptor binding
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms[3]. Second note to refd[4]
Seizure genesisa nd habituation of responseto sensorys timuli have been linked to nicotinic mechanisms (Marks et al., 1989;
Luntz-Leybman et al., 1992). These functions are closely associated
with the CA3 field (Schwartzkroin, 1986; Bickford-
Wimer et al., 1990). Nicotinic responsesa re mediated by two
major classeso f receptors, ganglionic type and neuromuscular
type. Pharmacological analysis of both seizure genesis and habituation
in rat brain implicates mediation by a neuromuscular
type (Miner and Collins, 1989; Luntz-Leybman et al., 1992).
These data are supported by the prominent binding of the neuromuscular-
type antagonist oc-bungarotoxin (a-BT) in the CA3
field of the hippocampus (Hunt and Schmidt, 1978; Segal et al.,
1978; Clarke et al., 1985
neuromuscular acetylcholine receptor bindingneuromuscular acetylcholine receptor binding
ReferencesReferences
| Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof.Andrea Gorrell. |