Sandbox 174: Difference between revisions
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=General Structure= | =General Structure= | ||
[[Image:figurename.png|thumb|Overall structure of Alpha-Bungarotoxin, with all individual residues visible]] | |||
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> per subunit. 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, E. (1979) in Lee,C Y (ed), ''Handbook of Experimental Pharmacology'' Springer-Verlag, Berlin Vol 52, pp 159-212;Low, B.W. (1979) In Lee,c Y (ed). ''Handbook of Experimental Pharmacology'' Springer-Verlag, Berlin, Vol 52, pp 213-257.</ref>. The importance of structure in binding has been tested by Love & Stroud (1986)<ref name="main">Love, A.R. and Stroud, R.M. (1986) The Crystal Structure of α-Bungarotoxin at 2.5 Å resolution: Relation to Solution Structure and Binding to Acetylcholine Receptor. ''Protein Eng'' '''1''', 37-46. </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> per subunit. 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, E. (1979) in Lee,C Y (ed), ''Handbook of Experimental Pharmacology'' Springer-Verlag, Berlin Vol 52, pp 159-212;Low, B.W. (1979) In Lee,c Y (ed). ''Handbook of Experimental Pharmacology'' Springer-Verlag, Berlin, Vol 52, pp 213-257.</ref>. The importance of structure in binding has been tested by Love & Stroud (1986)<ref name="main">Love, A.R. and Stroud, R.M. (1986) The Crystal Structure of α-Bungarotoxin at 2.5 Å resolution: Relation to Solution Structure and Binding to Acetylcholine Receptor. ''Protein Eng'' '''1''', 37-46. </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. | ||
The overall size of the molecule is 40 x 30 x 20 Å, with two outer loops folded toward one another. α-BGT is "flat" enough to contain no hydrophobic core, but does contain a few uncharged sidechain groupings<ref name="main">Love, A.R. and Stroud, R.M. (1986) The Crystal Structure of α-Bungarotoxin at 2.5 Å resolution: Relation to Solution Structure and Binding to Acetylcholine Receptor. ''Protein Eng'' '''1''', 37-46.</ref>. | The overall size of the molecule is 40 x 30 x 20 Å, with two outer loops folded toward one another. α-BGT is "flat" enough to contain no hydrophobic core, but does contain a few uncharged sidechain groupings<ref name="main">Love, A.R. and Stroud, R.M. (1986) The Crystal Structure of α-Bungarotoxin at 2.5 Å resolution: Relation to Solution Structure and Binding to Acetylcholine Receptor. ''Protein Eng'' '''1''', 37-46.</ref>. | ||
The protein is a dimer, and consists of two seperate subunits: | |||
<scene name='Sandbox_174/Domain_b/3'>Domain A</scene> | <scene name='Sandbox_174/Domain_b/3'>Domain A</scene> | ||
<scene name='Sandbox_174/Domain_a/3'>Domain B</scene> | <scene name='Sandbox_174/Domain_a/3'>Domain B</scene> | ||
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==neuromuscular acetylcholine receptor binding== | ==neuromuscular acetylcholine receptor binding== | ||
The irriversible and competitive binding to the acetylcholine receptor by α-BTG can be devastating to an organisms health due to its ability to block the receptors activity. | The irriversible and competitive binding to the acetylcholine receptor by α-BTG can be devastating to an organisms health due to its ability to block the receptors activity. | ||
==α7 nicotinic acetylcholine receptor binding== | ==α7 nicotinic acetylcholine receptor binding== | ||
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=References= | =References= | ||
<references/> | <references/> | ||
