https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Simon+LoewenProteopedia - User contributions [en]2026-09-14T21:32:28ZUser contributionsMediaWiki 1.43.8https://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1225329Sandbox Reserved 3282011-04-04T18:49:37Z<p>Simon Loewen: </p>
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{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=L-Histidinol Dehydrogenase=<br />
Histidine biosynthesis consists of 10 enzymatic reactions, of which the last two are facilitated by the oxidoreductase l-histidinol-dehydrogenase (HisD). These consist of sequential NAD-dependent oxidations of l-histidinol to l-histidinaldehyde, follows by the similar conversion to l-histidine<ref name="1kar"> PMID:11842181 </ref>. <br />
<br />
==Overall Structure==<br />
HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains (1 and 2) are within the globule, and domains 3 and 4 are found in the tail. The cores of both domains (residues 124–236 in domain 1 & 237–381 in domain 2) adopt incomplete Rossmann folds, which lack the last strand-helix hairpin<ref name="1kar" />. To carry out its function, HisD relies on the presence of one Zn2+ cation per monomer, not for catalysis, but for substrate binding. The Zn2+ cation is located at the bottom of the cavity occupied by the substrate and is octahedrally coordinated by four seperate residues. Along with Zn, the coordination of the substrate in the active site is assisted by the large degree of secondary structure present in the protein. The substrate binds in a deep pocket formed at the dimer interface between domains 1, 2, and 4, with most interactions being with residues at the N-terminal end of the β-sheet found within domain 2. Large amounts of secondary structure both in the form of <scene name='Sandbox_Reserved_328/Helices/1'>alpha helices</scene> and <scene name='Sandbox_Reserved_328/Beta_sheets/1'>beta sheets</scene> are present, and serve to provide a base for the overall structure of the molecule. <br />
Crystallogaphic data of HisD bound with NAD+ shows that the structure that allows the binding resembles to some extent the mode of binding observed in the aldehyde dehydrogenases, which have a six-residue insertion in the P loop. Overall, the method of binding differs from this class in that the insertions are usualy shorter, and translated approximately 10Å. <br />
<br />
==Enzymatic mechanism==<br />
[[Image:pathways.jpg]]<br />
<br />
The mechanism currently proposed by Teng and Grubmeyer<ref name="mech"> PMID:10353848 </ref> has been supported by structural data, and begins with the extraction of one proton and one hydride from L-histidinol<ref name="1kar" />. Next, the reduced NADH leaves and is replaced by another NAD+. The last step is a repetition of the first step. His-327 abstracts a proton from the hydroxyl group, and the second NAD+ molecule is reduced by a hydride. This leads to the formation of l-histidine.<br />
<br />
==Other information==<br />
===Gene Duplication===<br />
Domains 1 and 2 show high similarity in their cores, in a structural way rather than having large amounts of residues in common<ref name="1kar" />. This is also evident in the presense of hydrophobic residues forming the core of the domains. <br />
===Domain Swapping===<br />
Dimer formation most likely involves swapping of domains 3 and 4 between the two monomers, which explains the large amount of surface area (approximately 90%) buried upon dimerization. This type of domain swapping has been observed in other proteins as well<ref name="swap"> PMID:8580836 </ref>.<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1225325Sandbox Reserved 3282011-04-04T18:38:19Z<p>Simon Loewen: </p>
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{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=L-Histidinol Dehydrogenase=<br />
Histidine biosynthesis consists of 10 enzymatic reactions, of which the last two are facilitated by the oxidoreductase l-histidinol-dehydrogenase (HisD). These consist of sequential NAD-dependent oxidations of l-histidinol to l-histidinaldehyde, follows by the similar conversion to l-histidine<ref name="1kar"> PMID:11842181 </ref>. <br />
<br />
==Overall Structure==<br />
HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains (1 and 2) are within the globule, and domains 3 and 4 are found in the tail. The cores of both domains (residues 124–236 in domain 1 & 237–381 in domain 2) adopt incomplete Rossmann folds, which lack the last strand-helix hairpin<ref name="1kar" />. To carry out its function, HisD relies on the presence of one Zn2+ cation per monomer, not for catalysis, but for substrate binding. The Zn2+ cation is located at the bottom of the cavity occupied by the substrate and is octahedrally coordinated by four seperate residues. Along with Zn, the coordination of the substrate in the active site is assisted by the large degree of secondary structure present in the protein. The substrate binds in a deep pocket formed at the dimer interface between domains 1, 2, and 4, with most interactions being with residues at the N-terminal end of the β-sheet found within domain 2. Large amounts of secondary structure both in the form of <scene name='Sandbox_Reserved_328/Helices/1'>alpha helices</scene> and <scene name='Sandbox_Reserved_328/Beta_sheets/1'>beta sheets</scene> are present, and serve to provide a base for the overall structure of the molecule. <br />
<br />
==Enzymatic mechanism==<br />
[[Image:pathways.jpg]]<br />
<br />
The mechanism currently proposed by Teng and Grubmeyer<ref name="mech"> PMID:10353848 </ref> has been supported by structural data, and begins with the extraction of one proton and one hydride from L-histidinol<ref name="1kar" />. Next, the reduced NADH leaves and is replaced by another NAD+. The last step is a repetition of the first step. His-327 abstracts a proton from the hydroxyl group, and the second NAD+ molecule is reduced by a hydride. This leads to the formation of l-histidine.<br />
<br />
==Other information==<br />
===Gene Duplication===<br />
Domains 1 and 2 show high similarity in their cores, in a structural way rather than having large amounts of residues in common<ref name="1kar" />. This is also evident in the presense of hydrophobic residues forming the core of the domains. <br />
===Domain Swapping===<br />
Dimer formation most likely involves swapping of domains 3 and 4 between the two monomers, which explains the large amount of surface area (approximately 90%) buried upon dimerization. This type of domain swapping has been observed in other proteins as well<ref name="swap"> PMID:8580836 </ref>.<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1225322Sandbox Reserved 3282011-04-04T18:25:43Z<p>Simon Loewen: </p>
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{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=L-Histidinol Dehydrogenase=<br />
Histidine biosynthesis consists of 10 enzymatic reactions, of which the last two are facilitated by the oxidoreductase l-histidinol-dehydrogenase (HisD). These consist of sequential NAD-dependent oxidations of l-histidinol to l-histidinaldehyde, follows by the similar conversion to l-histidine<ref name="1kar"> PMID:11842181 </ref>. <br />
<br />
==Overall Structure==<br />
HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains (1 and 2) are within the globule, and domains 3 and 4 are found in the tail. The cores of both domains (residues 124–236 in domain 1 & 237–381 in domain 2) adopt incomplete Rossmann folds, which lack the last strand-helix hairpin<ref name="1kar" />. To carry out its function, HisD relies on the presence of one Zn2+ cation per monomer, not for catalysis, but for substrate binding. The Zn2+ cation is located at the bottom of the cavity occupied by the substrate and is octahedrally coordinated by four seperate residues. Along with Zn, the coordination of the substrate in the active site is assisted by the large degree of secondary structure present in the protein. The substrate binds in a deep pocket formed at the dimer interface between domains 1, 2, and 4, with most interactions being with residues at the N-terminal end of the β-sheet found within domain 2. Large amounts of secondary structure both in the form of <scene name='Sandbox_Reserved_328/Helices/1'>alpha helices</scene> and <scene name='Sandbox_Reserved_328/Beta_sheets/1'>beta sheets</scene> are present, and serve to provide a base for the overall structure of the molecule. <br />
<br />
==Enzymatic mechanism==<br />
[[Image:pathways.jpg]]<br />
<br />
The mechanism currently proposed by Teng and Grubmeyer<ref name="mech"> PMID:10353848 </ref> has been supported by structural data, and begins with the extraction of one proton and one hydride from L-histidinol<ref name="1kar" />.<br />
<br />
==Other information==<br />
===Domain swapping===<br />
Domains 1 and 2 show high similarity in their cores, in a structural way rather than having large amounts of residues in common<ref name="1kar" />. This is also evident in the presense of hydrophobic residues forming the core of the domains. <br />
===Domain Swapping===<br />
Dimer formation most likely involves swapping of domains 3 and 4 between the two monomers, which explains the large amount of surface area (approximately 90%) buried upon dimerization. This type of domain swapping has been observed in other proteins as well<ref name="swap"> PMID:8580836 </ref>.<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1225319Sandbox Reserved 3282011-04-04T18:13:15Z<p>Simon Loewen: </p>
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{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=L-Histidinol Dehydrogenase=<br />
The enzyme l-histidinol dehydrogenase (HisD)<br />
Basic information, current knowledge of areas found, etc. <br />
Structural<br />
==Overall Structure==<br />
HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains (1 and 2) are within the globule, and domains 3 and 4 are found in the tail. The cores of both domains (residues 124–236 in domain 1 & 237–381 in domain 2) adopt incomplete Rossmann folds, which lack the last strand-helix hairpin<ref name="1kar" />. To carry out its function, HisD relies on the presence of one Zn2+ cation per monomer, not for catalysis, but for substrate binding. The Zn2+ cation is located at the bottom of the cavity occupied by the substrate and is octahedrally coordinated by four seperate residues. Along with Zn, the coordination of the substrate in the active site is assisted by the large degree of secondary structure present in the protein. The substrate binds in a deep pocket formed at the dimer interface between domains 1, 2, and 4, with most interactions being with residues at the N-terminal end of the β-sheet found within domain 2. Large amounts of secondary structure both in the form of <scene name='Sandbox_Reserved_328/Helices/1'>alpha helices</scene> and <scene name='Sandbox_Reserved_328/Beta_sheets/1'>beta sheets</scene> are present, and serve to provide a base for the overall structure of the molecule. <br />
<br />
<br />
<br />
<br />
<br />
==Enzymatic mechanism==<br />
[[Image:pathways.jpg]]<br />
<br />
The mechanism currently proposed by Teng and Grubmeyer<ref name="mech"> PMID:10353848 </ref> has been supported by structural data, and begins with the extraction of one proton and one hydride from L-histidinol<ref name="1kar" />.<br />
<br />
<br />
==Other information==<br />
===Domain swapping===<br />
Domains 1 and 2 show high similarity in their cores, in a structural way rather than having large amounts of residues in common<ref name="1kar" />. This is also evident in the presense of hydrophobic residues forming the core of the domains. <br />
===Domain Swapping===<br />
Dimer formation most likely involves swapping of domains 3 and 4 between the two monomers, which explains the large amount of surface area (approximately 90%) buried upon dimerization. This type of domain swapping has been observed in other proteins as well<ref name="swap"> PMID:8580836 </ref>.<br />
<br />
<ref name="1kar"> PMID:11842181 </ref>. <br />
<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1225309Sandbox Reserved 3282011-04-04T17:59:47Z<p>Simon Loewen: </p>
<hr />
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<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=L-Histidinol Dehydrogenase=<br />
The enzyme l-histidinol dehydrogenase (HisD)<br />
Basic information, current knowledge of areas found, etc. <br />
Structural<br />
==Overall Structure==<br />
HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains (1 and 2) are within the globule, and domains 3 and 4 are found in the tail. The cores of both domains (residues 124–236 in domain 1 & 237–381 in domain 2) adopt incomplete Rossmann folds, which lack the last strand-helix hairpin<ref name="1kar" />. To carry out its function, HisD relies on the presence of one Zn2+ cation per monomer, not for catalysis, but for substrate binding. The Zn2+ cation is located at the bottom of the cavity occupied by the substrate and is octahedrally coordinated by four seperate residues. Along with Zn, the coordination of the substrate in the active site is assisted by the large degree of secondary structure present in the protein. The substrate binds in a deep pocket formed at the dimer interface between domains 1, 2, and 4, with most interactions being with residues at the N-terminal end of the β-sheet found within domain 2. Large amounts of secondary structure both in the form of <scene name='Sandbox_Reserved_328/Helices/1'>alpha helices</scene> and <scene name='Sandbox_Reserved_328/Beta_sheets/1'>beta sheets</scene> are present, and serve to provide a base for the overall structure of the molecule. <br />
<br />
<br />
<br />
<br />
<br />
==Enzymatic mechanism==<br />
[[Image:pathways.jpg]]<br />
<br />
The mechanism currently proposed by Teng and Grubmeyer<ref name="mech"> PMID:10353848 </ref> has been supported by structural data, and begins with the extraction of one proton and one hydride from L-histidinol<ref name="1kar" />.<br />
<br />
<br />
==Other information==<br />
===Domain swapping===<br />
<br />
<br />
<br />
<br />
<ref name="1kar"> PMID:11842181 </ref>. <br />
<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1225302Sandbox Reserved 3282011-04-04T17:48:19Z<p>Simon Loewen: </p>
<hr />
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{{Template:Sandbox_Reserved_BCMB307}}<br />
<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=L-Histidinol Dehydrogenase=<br />
The enzyme l-histidinol dehydrogenase (HisD)<br />
Basic information, current knowledge of areas found, etc. <br />
Structural<br />
==Overall Structure==<br />
HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains (1 and 2) are within the globule, and domains 3 and 4 are found in the tail. The cores of both domains (residues 124–236 in domain 1 & 237–381 in domain 2) adopt incomplete Rossmann folds, which lack the last strand-helix hairpin<ref name="1kar" />. To carry out its function, HisD relies on the presence of one Zn2+ cation per monomer, not for catalysis, but for substrate binding. The Zn2+ cation is located at the bottom of the cavity occupied by the substrate and is octahedrally coordinated by four seperate residues. Along with Zn, the coordination of the substrate in the active site is assisted by the large degree of secondary structure present in the protein. The substrate binds in a deep pocket formed at the dimer interface between domains 1, 2, and 4, with most interactions being with residues at the N-terminal end of the β-sheet found within domain 2. Large amounts of secondary structure both in the form of <scene name='Sandbox_Reserved_328/Helices/1'>alpha helices</scene> and <scene name='Sandbox_Reserved_328/Beta_sheets/1'>beta sheets</scene> are present, and serve to provide a base for the overall structure of the molecule. <br />
<br />
<br />
<br />
<br />
<br />
==Enzymatic mechanism==<br />
[[Image:pathways.jpg]]<br />
Proposed by Teng and Grubmeyer<ref name="mech"> PMID:10353848 </ref>. <br />
<br />
<br />
==Other information==<br />
<ref name="1kar" />. <br />
<br />
<br />
<ref name="1kar"> PMID:11842181 </ref>. <br />
<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1225301Sandbox Reserved 3282011-04-04T17:47:38Z<p>Simon Loewen: </p>
<hr />
<div><!-- PLEASE DO NOT DELETE THIS TEMPLATE --><br />
{{Template:Sandbox_Reserved_BCMB307}}<br />
<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=L-Histidinol Dehydrogenase=<br />
The enzyme l-histidinol dehydrogenase (HisD)<br />
Basic information, current knowledge of areas found, etc. <br />
Structural<br />
==Overall Structure==<br />
HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains (1 and 2) are within the globule, and domains 3 and 4 are found in the tail. The cores of both domains (residues 124–236 in domain 1 & 237–381 in domain 2) adopt incomplete Rossmann folds, which lack the last strand-helix hairpin<ref name="1kar" />. To carry out its function, HisD relies on the presence of one Zn2+ cation per monomer, not for catalysis, but for substrate binding. The Zn2+ cation is located at the bottom of the cavity occupied by the substrate and is octahedrally coordinated by four seperate residues. Along with Zn, the coordination of the substrate in the active site is assisted by the large degree of secondary structure present in the protein. The substrate binds in a deep pocket formed at the dimer interface between domains 1, 2, and 4, with most interactions being with residues at the N-terminal end of the β-sheet found within domain 2. Large amounts of secondary structure both in the form of <scene name='Sandbox_Reserved_328/Helices/1'>alpha helices</scene> and <scene name='Sandbox_Reserved_328/Beta_sheets/1'>beta sheets</scene> are present, and serve to provide a base for the overall structure of the molecule. <br />
<br />
<br />
<br />
<br />
<br />
==Enzymatic mechanism==<br />
[[Image:Example.jpg]]<br />
Proposed by Teng and Grubmeyer<ref name="mech"> PMID:10353848 </ref>. <br />
<br />
<br />
==Other information==<br />
<ref name="1kar" />. <br />
<br />
<br />
<ref name="1kar"> PMID:11842181 </ref>. <br />
<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1225297Sandbox Reserved 3282011-04-04T17:38:43Z<p>Simon Loewen: </p>
<hr />
<div><!-- PLEASE DO NOT DELETE THIS TEMPLATE --><br />
{{Template:Sandbox_Reserved_BCMB307}}<br />
<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=L-Histidinol Dehydrogenase=<br />
The enzyme l-histidinol dehydrogenase (HisD)<br />
Basic information, current knowledge of areas found, etc. <br />
Structural<br />
==Overall Structure==<br />
HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains (1 and 2) are within the globule, and domains 3 and 4 are found in the tail. The cores of both domains (residues 124–236 in domain 1 & 237–381 in domain 2) adopt incomplete Rossmann folds, which lack the last strand-helix hairpin<ref name="1kar" />. To carry out its function, HisD relies on the presence of one Zn2+ cation per monomer, not for catalysis, but for substrate binding. The Zn2+ cation is located at the bottom of the cavity occupied by the substrate and is octahedrally coordinated by four seperate residues. Along with Zn, the coordination of the substrate in the active site is assisted by the large degree of secondary structure present in the protein. The substrate binds in a deep pocket formed at the dimer interface between domains 1, 2, and 4, with most interactions being with residues at the N-terminal end of the β-sheet found within domain 2. Large amounts of secondary structure both in the form of <scene name='Sandbox_Reserved_328/Helices/1'>alpha helices</scene> and <scene name='Sandbox_Reserved_328/Beta_sheets/1'>beta sheets</scene> are present, and serve to provide a base for the overall structure of the molecule. <br />
<br />
<br />
<br />
<br />
<br />
==Enzymatic mechanism==<br />
[[Image:Example.jpg]]<br />
==Other information==<br />
<br />
<ref name="1kar" />. <br />
<ref name="1kar"> PMID:11842181 </ref>. <br />
<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=File:Pathways.jpg&diff=1225295File:Pathways.jpg2011-04-04T17:37:11Z<p>Simon Loewen: uploaded a new version of "Image:Pathways.jpg"</p>
<hr />
<div>== Licensing ==<br />
{{subst:Non-commercial from license selector}}</div>Simon Loewenhttps://proteopedia.org/index.php?title=File:Pathways.jpg&diff=1225290File:Pathways.jpg2011-04-04T17:31:26Z<p>Simon Loewen: </p>
<hr />
<div>== Licensing ==<br />
{{subst:Non-commercial from license selector}}</div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1225281Sandbox Reserved 3282011-04-04T17:21:03Z<p>Simon Loewen: </p>
<hr />
<div><!-- PLEASE DO NOT DELETE THIS TEMPLATE --><br />
{{Template:Sandbox_Reserved_BCMB307}}<br />
<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=L-Histidinol Dehydrogenase=<br />
The enzyme l-histidinol dehydrogenase (HisD)<br />
Basic information, current knowledge of areas found, etc. <br />
Structural<br />
==Overall Structure==<br />
HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains (1 and 2) are within the globule, and domains 3 and 4 are found in the tail. The cores of both domains (residues 124–236 in domain 1 & 237–381 in domain 2) adopt incomplete Rossmann folds, which lack the last strand-helix hairpin<ref name="1kar" />. To carry out its function, HisD relies on the presence of one Zn2+ cation per monomer, not for catalysis, but for substrate binding. The Zn2+ cation is located at the bottom of the cavity occupied by the substrate and is octahedrally coordinated by four seperate residues. Along with Zn, the coordination of the substrate in the active site is assisted by the large degree of secondary structure present in the protein. The substrate binds in a deep pocket formed at the dimer interface between domains 1, 2, and 4, with most interactions being with residues at the N-terminal end of the β-sheet found within domain 2. Large amounts of secondary structure both in the form of <scene name='Sandbox_Reserved_328/Helices/1'>alpha helices</scene> and <scene name='Sandbox_Reserved_328/Beta_sheets/1'>beta sheets</scene> are present, and serve to provide a base for the overall structure of the molecule. <br />
<br />
<br />
<br />
<br />
<br />
==Enzymatic mechanism==<br />
<br />
==Other information==<br />
<br />
<ref name="1kar" />. <br />
<ref name="1kar"> PMID:11842181 </ref>. <br />
<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1224283Sandbox Reserved 3282011-04-03T06:12:38Z<p>Simon Loewen: </p>
<hr />
<div><!-- PLEASE DO NOT DELETE THIS TEMPLATE --><br />
{{Template:Sandbox_Reserved_BCMB307}}<br />
<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=L-Histidinol Dehydrogenase=<br />
The enzyme l-histidinol dehydrogenase (HisD)<br />
<br />
ALL INFORMATION IN HERE!!! sub-headings for topics of interest (mechanism, binding sites, etc.) Basic information, current knowledge of areas found, etc. <br />
Structural<br />
==Overall Structure==<br />
HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains (1 and 2) are within the globule, and domains 3 and 4 are found in the tail. The cores of both domains (residues 124–236 in domain 1 & 237–381 in domain 2) adopt incomplete Rossmann folds, which lack the last strand-helix hairpin<ref name="1kar" />. To carry out its function, HisD relies on the presence of one Zn2+ cation per monomer, not for catalysis, but for substrate binding. The Zn2+ cation is located at the bottom of the cavity occupied by the substrate and is octahedrally coordinated by four seperate residues. Along with Zn, the coordination of the substrate in the active site is assisted by the large degree of secondary structure present in the protein. The substrate binds in a deep pocket formed at the dimer interface between domains 1, 2, and 4, with most interactions being with residues at the N-terminal end of the β-sheet found within domain 2. Large amounts of secondary structure both in the form of <scene name='Sandbox_Reserved_328/Helices/1'>alpha helices</scene> and <scene name='Sandbox_Reserved_328/Beta_sheets/1'>beta sheets</scene> are present, and serve to provide a base for the overall structure of the molecule. <br />
<br />
<br />
<br />
<br />
<br />
==Enzymatic mechanism==<br />
<br />
==Other information??==<br />
<br />
<ref name="1kar" />. <br />
<ref name="1kar"> PMID:11842181 </ref>. <br />
<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1224278Sandbox Reserved 3282011-04-03T05:38:13Z<p>Simon Loewen: </p>
<hr />
<div><!-- PLEASE DO NOT DELETE THIS TEMPLATE --><br />
{{Template:Sandbox_Reserved_BCMB307}}<br />
<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=L-Histidinol Dehydrogenase=<br />
The enzyme l-histidinol dehydrogenase (HisD)<br />
<br />
ALL INFORMATION IN HERE!!! sub-headings for topics of interest (mechanism, binding sites, etc.) Basic information, current knowledge of areas found, etc. <br />
Structural<br />
==Overall Structure==<br />
HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains (1 and 2) are within the globule, and domains 3 and 4 are found in the tail. The cores of both domains (residues 124–236 in domain 1 & 237–381 in domain 2) adopt incomplete Rossmann folds, which lack the last strand-helix hairpin<ref name="1kar" />. To carry out its function, HisD relies on the presence of one Zn2+ cation per monomer, not for catalysis, but for substrate binding. <br />
<br />
<scene name='Sandbox_Reserved_328/Beta_sheets/1'>Beta Sheets</scene><br />
<br />
<scene name='Sandbox_Reserved_328/Helices/1'>alpha helices</scene><br />
<br />
==Enzymatic mechanism==<br />
<br />
==Other information??==<br />
<br />
<ref name="1kar" />. <br />
<ref name="1kar"> PMID:11842181 </ref>. <br />
<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1224273Sandbox Reserved 3282011-04-03T05:25:03Z<p>Simon Loewen: </p>
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{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=L-Histidinol Dehydrogenase=<br />
The enzyme l-histidinol dehydrogenase (HisD)<br />
<br />
ALL INFORMATION IN HERE!!! sub-headings for topics of interest (mechanism, binding sites, etc.) Basic information, current knowledge of areas found, etc. <br />
Structural<br />
==Overall Structure==<br />
HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains (1 and 2) are within the globule, and domains 3 and 4 are found in the tail. <br />
<br />
<scene name='Sandbox_Reserved_328/Beta_sheets/1'>Beta Sheets</scene><br />
<br />
<scene name='Sandbox_Reserved_328/Helices/1'>alpha helices</scene><br />
<br />
==Enzymatic mechanism==<br />
<br />
==Other information??==<br />
<br />
<ref name="1kar" />. <br />
<ref name="1kar"> PMID:11842181 </ref>. <br />
<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1224271Sandbox Reserved 3282011-04-03T05:18:16Z<p>Simon Loewen: </p>
<hr />
<div><!-- PLEASE DO NOT DELETE THIS TEMPLATE --><br />
{{Template:Sandbox_Reserved_BCMB307}}<br />
<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=L-Histidinol Dehydrogenase=<br />
The enzyme l-histidinol dehydrogenase (HisD)<br />
<br />
ALL INFORMATION IN HERE!!! sub-headings for topics of interest (mechanism, binding sites, etc.) Basic information, current knowledge of areas found, etc. <br />
Structural<br />
==Overall Structure==<br />
HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains (1 and 2) are within the globule, and domains 3 and 4 are found in the tail. <br />
<br />
<scene name='Sandbox_Reserved_328/Beta_sheets/1'>Beta Sheets</scene><br />
<br />
==Enzymatic mechanism==<br />
<br />
==Other information??==<br />
<br />
<ref name="1kar" />. <br />
<ref name="1kar"> PMID:11842181 </ref>. <br />
<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1224252Sandbox Reserved 3282011-04-03T04:26:07Z<p>Simon Loewen: </p>
<hr />
<div><!-- PLEASE DO NOT DELETE THIS TEMPLATE --><br />
{{Template:Sandbox_Reserved_BCMB307}}<br />
<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=L-Histidinol Dehydrogenase=<br />
The enzyme l-histidinol dehydrogenase (HisD)<br />
<br />
ALL INFORMATION IN HERE!!! sub-headings for topics of interest (mechanism, binding sites, etc.) Basic information, current knowledge of areas found, etc. <br />
Structural<br />
==Overall Structure==<br />
HisD is a homodimer, with each subunit consisting of a globule segment, and an extending tail. The two larger domains <scene name='Globule Domains'>(1 and 2)</scene>. are within the globule, and domains 3 and 4 are found in the tail. <br />
<br />
==Enzymatic mechanism==<br />
<br />
==Other information??==<br />
<br />
<ref name="1kar" />. <br />
<ref name="1kar"> PMID:11842181 </ref>. <br />
<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1224244Sandbox Reserved 3282011-04-03T03:54:53Z<p>Simon Loewen: </p>
<hr />
<div><!-- PLEASE DO NOT DELETE THIS TEMPLATE --><br />
{{Template:Sandbox_Reserved_BCMB307}}<br />
<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=L-Histidinol Dehydrogenase=<br />
ALL INFORMATION IN HERE!!! sub-headings for topics of interest (mechanism, binding sites, etc.) Basic information, current knowledge of areas found, etc. <br />
<br />
==Enzymatic mechanism==<br />
<br />
==Other information??==<br />
<br />
Sec structure <ref name="1kar" />. <br />
<Structure load='XXXX' size='500' frame='true' align='RIGHT' caption='Insert caption here' scene='Insert optional scene name here' /><br />
<ref name="1kar"> PMID:11842181 </ref>. <br />
==Structure==<br />
disulphides, secondary, etc.<br />
<ref name="supersecondary"> PMID:11111111 </ref> <br />
<br />
<br />
<br />
==Function==<br />
evolutionary purpose?<br />
<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1224063Sandbox Reserved 3282011-04-02T21:51:04Z<p>Simon Loewen: </p>
<hr />
<div><!-- PLEASE DO NOT DELETE THIS TEMPLATE --><br />
{{Template:Sandbox_Reserved_BCMB307}}<br />
<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=My Protein of Interest (MPI)=<br />
Basic information, current knowledge of areas found, etc. <br />
<br />
==Picture==<br />
Sec structure <ref name="1kar" />. <br />
<Structure load='XXXX' size='500' frame='true' align='RIGHT' caption='Insert caption here' scene='Insert optional scene name here' /><br />
<ref name="1kar"> PMID:11842181 </ref>. <br />
==Structure==<br />
disulphides, secondary, etc.<br />
<ref name="supersecondary"> PMID:11111111 </ref> <br />
<br />
<br />
<br />
==Function==<br />
evolutionary purpose?<br />
<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1224059Sandbox Reserved 3282011-04-02T21:47:18Z<p>Simon Loewen: </p>
<hr />
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{{Template:Sandbox_Reserved_BCMB307}}<br />
<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=My Protein of Interest (MPI)=<br />
Basic information, current knowledge of areas found, etc. <br />
<br />
==Picture==<br />
Sec structure <ref name="1kar" />. <br />
<Structure load='XXXX' size='500' frame='true' align='RIGHT' caption='Insert caption here' scene='Insert optional scene name here' /><br />
<ref name="1kar"> PMID:11842181 </ref>. <br />
==Structure==<br />
disulphides, secondary, etc.<br />
<ref name="superseconday"> PMID: </ref> <br />
<br />
<br />
<br />
==Function==<br />
evolutionary purpose?<br />
<br />
<br />
==References==<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1219767Sandbox Reserved 3282011-03-25T17:52:30Z<p>Simon Loewen: </p>
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{{Template:Sandbox_Reserved_BCMB307}}<br />
<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
{{STRUCTURE_1kar| PDB=1kar | SCENE= }}<br />
=My Protein of Interest (MPI)=<br />
Basic information, current knowledge of areas found, etc. <br />
<br />
==Picture==<br />
<br />
<Structure load='XXXX' size='500' frame='true' align='RIGHT' caption='Insert caption here' scene='Insert optional scene name here' /><br />
<ref name="seconday structure" /><br />
<br />
==Structure==<br />
disulphides, secondary, etc.<br />
<ref name="superseconday"> PMID: </ref> <br />
<br />
<br />
<br />
==Function==<br />
evolutionary purpose?<br />
<br />
<br />
==References==<br />
<references PUB MED IDS/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1216461Sandbox Reserved 3282011-03-18T23:01:41Z<p>Simon Loewen: </p>
<hr />
<div><!-- PLEASE DO NOT DELETE THIS TEMPLATE --><br />
{{Template:Sandbox_Reserved_BCMB307}}<br />
<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
=My Protein of Interest (MPI)=<br />
Basic information, current knowledge of areas found, etc. <br />
<br />
==Picture==<br />
<br />
<Structure load='XXXX' size='500' frame='true' align='RIGHT' caption='Insert caption here' scene='Insert optional scene name here' /><br />
<ref name="seconday structure" /><br />
<br />
==Structure==<br />
disulphides, secondary, etc.<br />
<ref name="superseconday"> PMID: </ref> <br />
<br />
<br />
<br />
==Function==<br />
evolutionary purpose?<br />
<br />
<br />
==References==<br />
<references PUB MED IDS/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1216460Sandbox Reserved 3282011-03-18T23:00:43Z<p>Simon Loewen: </p>
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<div><!-- PLEASE DO NOT DELETE THIS TEMPLATE --><br />
{{Template:Sandbox_Reserved_BCMB307}}<br />
<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
=My Protein of Interest (MPI)=<br />
Basic information, current knowledge of areas found, etc. <br />
<br />
==Picture==<br />
<br />
<Structure load='XXXX' size='500' frame='true' align='RIGHT' caption='Insert caption here' scene='Insert optional scene name here' /><br />
<ref name="superseconday"> PMID: </ref> <br />
<ref name="seconday structure" /><br />
<br />
==Structure==<br />
disulphides, secondary, etc.<br />
<br />
<br />
==Function==<br />
evolutionary purpose?<br />
<br />
<br />
==References==<br />
<references PUB MED IDS></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_Reserved_328&diff=1216459Sandbox Reserved 3282011-03-18T22:59:04Z<p>Simon Loewen: </p>
<hr />
<div><!-- PLEASE DO NOT DELETE THIS TEMPLATE --><br />
{{Template:Sandbox_Reserved_BCMB307}}<br />
<!-- PLEASE ADD YOUR CONTENT BELOW HERE --><br />
=My Protein of Interest (MPI)=<br />
Basic information, current knowledge of areas found, etc. <br />
<br />
==Picture==<br />
<br />
<Structure load='XXXX' size='500' frame='true' align='RIGHT' caption='Insert caption here' scene='Insert optional scene name here' /><br />
<br />
==Structure==<br />
disulphides, secondary, etc.<br />
<br />
<ref name="superseconday"> PMID: </ref> <br />
<ref name="seconday structure" /><br />
<br />
==Function==<br />
evolutionary purpose?<br />
<br />
<br />
==References==<br />
<references/> PUBMED IDS!!!</div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1076915Sandbox 1742010-04-14T18:37:00Z<p>Simon Loewen: Removing all content from page</p>
<hr />
<div></div>Simon Loewenhttps://proteopedia.org/index.php?title=Alpha-bungarotoxin&diff=1076914Alpha-bungarotoxin2010-04-14T18:35:29Z<p>Simon Loewen: New page: {{STRUCTURE_2abx | PDB=2abx | SCENE= }} =Alpha-Bungarotoxin= Alpha-Bungarotoxin (α-BGT) is a nicotinic cholinergic antagonist that is found within the venom of ''Bungarus multicinctus...</p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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">PMID: 3507686</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.<br />
<br />
=General Structure=<br />
[[Image:figurename.png| left| thumb |Overall structure of Alpha-Bungarotoxin, with all individual residues visible]]<br />
<br />
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.<br />
<br />
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>.<br />
The protein is a dimer, and consists of two seperate subunits:<br />
<scene name='Sandbox_174/Domain_b/4'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/4'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bonds present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<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 three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<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>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref>PMID: 5554293</ref> and strong acids<ref>Chiceportiche, R. Rochat, C. Sampien, F. Lazdunski, M. (1972) ''Biochemistry'' '''14''', 2081-2091;Chen, Y.H. Tai, J.C. Huand, W.J. Lau, M.Z. Hung, M.C. Lai, M.D. Yang, J.T. (1982) ''Biochemistry'' '''21''' 2592-2600</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<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>, classifying the molecule as a postsynaptic neurotoxin. <br />
==Neuromuscular acetylcholine receptor binding==<br />
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. Released acetylcholine diffuses across the gap separating nerve and muscle cells, interacting with specific receptors associated with the postsynaptic muscle membrane. This produces an increase in permeability in the membrane to both sodium and potassium ions. Toxins purified from the venoms of ''Bungarus multicinctus'' disrupt neuromuscular transmission by blocking the postsynaptic response to acetylcholine. In addition, a-bungarotoxin blocks the response to acetylcholine of denervated muscle fibers <ref>PMID: 4333037</ref><br />
<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Response to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>PMID: 8478687</ref>, which are mediated by two major classes of receptors: Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref>PMID: 2813485</ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref>PMID: 626914</ref>.<br />
<br />
<br />
=References=<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1064493Sandbox 1742010-03-31T19:29:08Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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">PMID: 3507686</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.<br />
<br />
=General Structure=<br />
[[Image:figurename.png| left| thumb |Overall structure of Alpha-Bungarotoxin, with all individual residues visible]]<br />
<br />
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.<br />
<br />
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>.<br />
The protein is a dimer, and consists of two seperate subunits:<br />
<scene name='Sandbox_174/Domain_b/4'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/4'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<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 three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<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>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref>PMID: 5554293</ref> and strong acids<ref>Chiceportiche, R. Rochat, C. Sampien, F. Lazdunski, M. (1972) ''Biochemistry'' '''14''', 2081-2091;Chen, Y.H. Tai, J.C. Huand, W.J. Lau, M.Z. Hung, M.C. Lai, M.D. Yang, J.T. (1982) ''Biochemistry'' '''21''' 2592-2600</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<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>, classifying the molecule as a postsynaptic neurotoxin. <br />
==neuromuscular acetylcholine receptor binding==<br />
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. Released acetylcholine diffuses across the gap separating nerve and muscle cells, interacting with specific receptors associated with the postsynaptic muscle membrane. This produces an increase in permeability in the membrane to both sodium and potassium ions. Toxins purified from the venoms of ''Bungarus multicinctus'' disrupt neuromuscular transmission by blocking the postsynaptic response to acetylcholine. In addition, a-bungarotoxin blocks the response to acetylcholine of denervated muscle fibers <ref>PMID: 4333037</ref><br />
<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Response to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>PMID: 8478687</ref>, which are mediated by two major classes of receptors: Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref>PMID: 2813485</ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref>PMID: 626914</ref>.<br />
<br />
<br />
=References=<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1064487Sandbox 1742010-03-31T19:15:16Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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">PMID: 3507686</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.<br />
<br />
=General Structure=<br />
[[Image:figurename.png| left| thumb |Overall structure of Alpha-Bungarotoxin, with all individual residues visible]]<br />
<br />
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.<br />
<br />
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>.<br />
The protein is a dimer, and consists of two seperate subunits:<br />
<scene name='Sandbox_174/Domain_b/4'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/4'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<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 three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<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>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref>PMID: 5554293</ref> and strong acids<ref>Chiceportiche, R. Rochat, C. Sampien, F. Lazdunski, M. (1972) ''Biochemistry'' '''14''', 2081-2091;Chen, Y.H. Tai, J.C. Huand, W.J. Lau, M.Z. Hung, M.C. Lai, M.D. Yang, J.T. (1982) ''Biochemistry'' '''21''' 2592-2600</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<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>, classifying the molecule as a postsynaptic neurotoxin. <br />
==neuromuscular acetylcholine receptor binding==<br />
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. <br />
<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Response to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>PMID: 8478687</ref>, which are mediated by two major classes of receptors: Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref>PMID: 2813485</ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref>PMID: 626914</ref>.<br />
<br />
<br />
=References=<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1064486Sandbox 1742010-03-31T19:14:44Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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">PMID: 3507686</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.<br />
<br />
=General Structure=<br />
[[Image:figurename.png| left| thumb |Overall structure of Alpha-Bungarotoxin, with all individual residues visible]]<br />
<br />
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.<br />
<br />
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>.<br />
The protein is a dimer, and consists of two seperate subunits:<br />
<scene name='Sandbox_174/Domain_b/4'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/4'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<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 three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<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>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref>PMID: 5554293</ref> and strong acids<ref>Chiceportiche, R. Rochat, C. Sampien, F. Lazdunski, M. (1972) ''Biochemistry'' '''14''', 2081-2091;Chen, Y.H. Tai, J.C. Huand, W.J. Lau, M.Z. Hung, M.C. Lai, M.D. Yang, J.T. (1982) ''Biochemistry'' '''21''' 2592-2600</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<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>, classifying the molecule as a postsynaptic neurotoxin. <br />
==neuromuscular acetylcholine receptor binding==<br />
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. <br />
<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Response to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>PMID: 8478687</ref>, which are mediated by two major classes of receptors: Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref>PMID: 2813485 + PMID: 1525643</ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref>PMID: 626914, PMID: 656919</ref>.<br />
<br />
<br />
=References=<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1064483Sandbox 1742010-03-31T19:11:30Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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">PMID: 3507686</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.<br />
<br />
=General Structure=<br />
[[Image:figurename.png| left| thumb |Overall structure of Alpha-Bungarotoxin, with all individual residues visible]]<br />
<br />
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.<br />
<br />
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>.<br />
The protein is a dimer, and consists of two seperate subunits:<br />
<scene name='Sandbox_174/Domain_b/4'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/4'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<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 three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<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>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref>PMID: 5554293</ref> and strong acids<ref>Chiceportiche, R. Rochat, C. Sampien, F. Lazdunski, M. (1972) ''Biochemistry'' '''14''', 2081-2091;Chen, Y.H. Tai, J.C. Huand, W.J. Lau, M.Z. Hung, M.C. Lai, M.D. Yang, J.T. (1982) ''Biochemistry'' '''21''' 2592-2600</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<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>, classifying the molecule as a postsynaptic neurotoxin. <br />
==neuromuscular acetylcholine receptor binding==<br />
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. <br />
<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Response to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>PMID: 8478687</ref>, which are mediated by two major classes of receptors: Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref>PMID: 2813485;PMID: 1525643</ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref>PMID: 626914;PMID: 656919</ref>.<br />
<br />
<br />
=References=<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1064477Sandbox 1742010-03-31T18:57:39Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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. 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> 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.<br />
<br />
=General Structure=<br />
[[Image:figurename.png| left| thumb |Overall structure of Alpha-Bungarotoxin, with all individual residues visible]]<br />
<br />
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.<br />
<br />
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>.<br />
The protein is a dimer, and consists of two seperate subunits:<br />
<scene name='Sandbox_174/Domain_b/4'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/4'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<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 three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<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>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref> Tu, A.T. and Hong, B.S (1971) ''J Biol Chem''. '''246''', 2772-2779;Yang, C.C. ''Toxicon'' '''12''', 1-43.</ref> and strong acids<ref>Chiceportiche, R. Rochat, C. Sampien, F. Lazdunski, M. (1972) ''Biochemistry'' '''14''', 2081-2091;Chen, Y.H. Tai, J.C. Huand, W.J. Lau, M.Z. Hung, M.C. Lai, M.D. Yang, J.T. (1982) ''Biochemistry'' '''21''' 2592-2600</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<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>, classifying the molecule as a postsynaptic neurotoxin. <br />
==neuromuscular acetylcholine receptor binding==<br />
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. <br />
<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Response to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>Freedman, R. Wetmore, C. Stromberg, I. Leonard, S. Olsona, L. (1993) Alpha-Bungarotoxin Binding to Hippocampal Interneurons: lmmunocytochemical Characterization and Effects on Growth Factor Expression. ''Journal of Neuroscience'' 13:1965-1975. </ref>, which are mediated by two major classes of receptors: Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref> Miner L.L. Collins A.C. (1989) Strain comparison of nicotine-induced seizure sensitivity and nicotinic receptors. ''Pharmacol Biochem Behav'' '''33''', 469-475;Luntz-Leybman, V. Bickford, P. Freedman, R. (1992) Cholinergic gating of response to auditory stimuli in rat hippocampus. ''Brain Res'' '''587''', 130-l-36.</ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref> Hunt, S.P. Schmidt, J. (1978) The electron microscopic autoradiographic localization of alpha-bungarotoxin binding sites within the central nervous system of the rat: ''Brain Res'' '''142''', 152-l 59;Segal, M. Dudai, Y. Amsterdam, A. (1978) Distribution of cu-bungarotoxin-<br />
binding cholinergic nicotinic receptor in rat brain. ''Brain Res'' '''148''', 105-l 19.</ref>.<br />
<br />
<br />
=References=<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1064408Sandbox 1742010-03-31T16:50:58Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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. 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> 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.<br />
<br />
=General Structure=<br />
<br />
<br />
[[Image:figurename.png|thumb|Overall structure of Alpha-Bungarotoxin, with all individual residues visible]]<br />
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.<br />
<br />
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>.<br />
The protein is a dimer, and consists of two seperate subunits:<br />
<scene name='Sandbox_174/Domain_b/3'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/3'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<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 three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<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>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref> Tu, A.T. and Hong, B.S (1971) ''J Biol Chem''. '''246''', 2772-2779;Yang, C.C. ''Toxicon'' '''12''', 1-43.</ref> and strong acids<ref>Chiceportiche, R. Rochat, C. Sampien, F. Lazdunski, M. (1972) ''Biochemistry'' '''14''', 2081-2091;Chen, Y.H. Tai, J.C. Huand, W.J. Lau, M.Z. Hung, M.C. Lai, M.D. Yang, J.T. (1982) ''Biochemistry'' '''21''' 2592-2600</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<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>, classifying the molecule as a postsynaptic neurotoxin. <br />
==neuromuscular acetylcholine receptor binding==<br />
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. <br />
<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Response to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>Freedman, R. Wetmore, C. Stromberg, I. Leonard, S. Olsona, L. (1993) Alpha-Bungarotoxin Binding to Hippocampal Interneurons: lmmunocytochemical Characterization and Effects on Growth Factor Expression. ''Journal of Neuroscience'' 13:1965-1975. </ref>, which are mediated by two major classes of receptors: Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref> Miner L.L. Collins A.C. (1989) Strain comparison of nicotine-induced seizure sensitivity and nicotinic receptors. ''Pharmacol Biochem Behav'' '''33''', 469-475;Luntz-Leybman, V. Bickford, P. Freedman, R. (1992) Cholinergic gating of response to auditory stimuli in rat hippocampus. ''Brain Res'' '''587''', 130-l-36.</ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref> Hunt, S.P. Schmidt, J. (1978) The electron microscopic autoradiographic localization of alpha-bungarotoxin binding sites within the central nervous system of the rat: ''Brain Res'' '''142''', 152-l 59;Segal, M. Dudai, Y. Amsterdam, A. (1978) Distribution of cu-bungarotoxin-<br />
binding cholinergic nicotinic receptor in rat brain. ''Brain Res'' '''148''', 105-l 19.</ref>.<br />
<br />
<br />
=References=<br />
<references/></div>Simon Loewenhttps://proteopedia.org/index.php?title=File:Figurename.png&diff=1064407File:Figurename.png2010-03-31T16:48:00Z<p>Simon Loewen: </p>
<hr />
<div></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1064406Sandbox 1742010-03-31T16:47:31Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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. 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> 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.<br />
<br />
=General Structure=<br />
[[Image:figurename.png|thumb|Overall structure of Alpha-Bungarotoxin, with all individual residues visible]]<br />
<br />
<br />
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.<br />
<br />
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>.<br />
<br />
<scene name='Sandbox_174/Domain_b/3'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/3'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<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 three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<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>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref> Tu, A.T. and Hong, B.S (1971) ''J Biol Chem''. '''246''', 2772-2779;Yang, C.C. ''Toxicon'' '''12''', 1-43.</ref> and strong acids<ref>Chiceportiche, R. Rochat, C. Sampien, F. Lazdunski, M. (1972) ''Biochemistry'' '''14''', 2081-2091;Chen, Y.H. Tai, J.C. Huand, W.J. Lau, M.Z. Hung, M.C. Lai, M.D. Yang, J.T. (1982) ''Biochemistry'' '''21''' 2592-2600</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<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>, classifying the molecule as a postsynaptic neurotoxin. <br />
==neuromuscular acetylcholine receptor binding==<br />
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. <br />
<br />
http://www.ncbi.nlm.nih.gov/pubmed/12885641<br />
<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Response to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>Freedman, R. Wetmore, C. Stromberg, I. Leonard, S. Olsona, L. (1993) Alpha-Bungarotoxin Binding to Hippocampal Interneurons: lmmunocytochemical Characterization and Effects on Growth Factor Expression. ''Journal of Neuroscience'' 13:1965-1975. </ref>, which are mediated by two major classes of receptors: Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref> Miner L.L. Collins A.C. (1989) Strain comparison of nicotine-induced seizure sensitivity and nicotinic receptors. ''Pharmacol Biochem Behav'' '''33''', 469-475;Luntz-Leybman, V. Bickford, P. Freedman, R. (1992) Cholinergic gating of response to auditory stimuli in rat hippocampus. ''Brain Res'' '''587''', 130-l-36.</ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref> Hunt, S.P. Schmidt, J. (1978) The electron microscopic autoradiographic localization of alpha-bungarotoxin binding sites within the central nervous system of the rat: ''Brain Res'' '''142''', 152-l 59;Segal, M. Dudai, Y. Amsterdam, A. (1978) Distribution of cu-bungarotoxin-<br />
binding cholinergic nicotinic receptor in rat brain. ''Brain Res'' '''148''', 105-l 19.</ref>.<br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1061549Sandbox 1742010-03-26T21:57:20Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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. 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> 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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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.<br />
<br />
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>.<br />
<br />
<scene name='Sandbox_174/Domain_b/3'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/3'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<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 three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<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>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref> Tu, A.T. and Hong, B.S (1971) ''J Biol Chem''. '''246''', 2772-2779;Yang, C.C. ''Toxicon'' '''12''', 1-43.</ref> and strong acids<ref>Chiceportiche, R. Rochat, C. Sampien, F. Lazdunski, M. (1972) ''Biochemistry'' '''14''', 2081-2091;Chen, Y.H. Tai, J.C. Huand, W.J. Lau, M.Z. Hung, M.C. Lai, M.D. Yang, J.T. (1982) ''Biochemistry'' '''21''' 2592-2600</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<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>, classifying the molecule as a postsynaptic neurotoxin. <br />
==neuromuscular acetylcholine receptor binding==<br />
The irriversable 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. <br />
<br />
http://www.ncbi.nlm.nih.gov/pubmed/12885641<br />
<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>Freedman, R. Wetmore, C. Stromberg, I. Leonard, S. Olsona, L. (1993) Alpha-Bungarotoxin Binding to Hippocampal Interneurons: lmmunocytochemical Characterization and Effects on Growth Factor Expression. ''Journal of Neuroscience'' 13:1965-1975. </ref>, which are mediated by two major classes of receptors: Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref> Miner L.L. Collins A.C. (1989) Strain comparison of nicotine-induced seizure sensitivity and nicotinic receptors. ''Pharmacol Biochem Behav'' '''33''', 469-475;Luntz-Leybman, V. Bickford, P. Freedman, R. (1992) Cholinergic gating of response to auditory stimuli in rat hippocampus. ''Brain Res'' '''587''', 130-l-36.</ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref> Hunt, S.P. Schmidt, J. (1978) The electron microscopic autoradiographic localization of alpha-bungarotoxin binding sites within the central nervous system of the rat: ''Brain Res'' '''142''', 152-l 59;Segal, M. Dudai, Y. Amsterdam, A. (1978) Distribution of cu-bungarotoxin-<br />
binding cholinergic nicotinic receptor in rat brain. ''Brain Res'' '''148''', 105-l 19.</ref>.<br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1061543Sandbox 1742010-03-26T21:32:01Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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. 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> 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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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.<br />
<br />
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>.<br />
<br />
<scene name='Sandbox_174/Domain_b/3'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/3'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<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 three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<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>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref> Tu, A.T. and Hong, B.S (1971) ''J Biol Chem''. '''246''', 2772-2779;Yang, C.C. ''Toxicon'' '''12''', 1-43.</ref> and strong acids<ref>Chiceportiche, R. Rochat, C. Sampien, F. Lazdunski, M. (1972) ''Biochemistry'' '''14''', 2081-2091;Chen, Y.H. Tai, J.C. Huand, W.J. Lau, M.Z. Hung, M.C. Lai, M.D. Yang, J.T. (1982) ''Biochemistry'' '''21''' 2592-2600</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<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>, classifying the molecule as a postsynaptic neurotoxin. <br />
==neuromuscular acetylcholine receptor binding==<br />
===blah===<br />
<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>Freedman, R. Wetmore, C. Stromberg, I. Leonard, S. Olsona, L. (1993) Alpha-Bungarotoxin Binding to Hippocampal Interneurons: lmmunocytochemical Characterization and Effects on Growth Factor Expression. ''Journal of Neuroscience'' 13:1965-1975. </ref>, which are mediated by two major classes of receptors: Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref> Miner L.L. Collins A.C. (1989) Strain comparison of nicotine-induced seizure sensitivity and nicotinic receptors. ''Pharmacol Biochem Behav'' '''33''', 469-475;Luntz-Leybman, V. Bickford, P. Freedman, R. (1992) Cholinergic gating of response to auditory stimuli in rat hippocampus. ''Brain Res'' '''587''', 130-l-36.</ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref> Hunt, S.P. Schmidt, J. (1978) The electron microscopic autoradiographic localization of alpha-bungarotoxin binding sites within the central nervous system of the rat: ''Brain Res'' '''142''', 152-l 59;Segal, M. Dudai, Y. Amsterdam, A. (1978) Distribution of cu-bungarotoxin-<br />
binding cholinergic nicotinic receptor in rat brain. ''Brain Res'' '''148''', 105-l 19.</ref>.<br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1061538Sandbox 1742010-03-26T21:16:54Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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. 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> 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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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, 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.<br />
<br />
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>.<br />
<br />
<scene name='Sandbox_174/Domain_b/3'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/3'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<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 three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<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>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref> Tu, A.T. and Hong, B.S (1971) ''J Biol Chem''. '''246''', 2772-2779;Yang, C.C. ''Toxicon'' '''12''', 1-43.</ref> and strong acids<ref>Chiceportiche, R. Rochat, C. Sampien, F. Lazdunski, M. (1972) ''Biochemistry'' '''14''', 2081-2091;Chen, Y.H. Tai, J.C. Huand, W.J. Lau, M.Z. Hung, M.C. Lai, M.D. Yang, J.T. (1982) ''Biochemistry'' '''21''' 2592-2600</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<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>. <br />
==neuromuscular acetylcholine receptor binding==<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>Freedman, R. Wetmore, C. Stromberg, I. Leonard, S. Olsona, L. (1993) Alpha-Bungarotoxin Binding to Hippocampal Interneurons: lmmunocytochemical Characterization and Effects on Growth Factor Expression. ''Journal of Neuroscience'' 13:1965-1975. </ref>, which are mediated by two major classes of receptors: Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref> Miner L.L. Collins A.C. (1989) Strain comparison of nicotine-induced seizure sensitivity and nicotinic receptors. ''Pharmacol Biochem Behav'' '''33''', 469-475;Luntz-Leybman, V. Bickford, P. Freedman, R. (1992) Cholinergic gating of response to auditory stimuli in rat hippocampus. ''Brain Res'' '''587''', 130-l-36.</ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref> Hunt, S.P. Schmidt, J. (1978) The electron microscopic autoradiographic localization of alpha-bungarotoxin binding sites within the central nervous system of the rat: ''Brain Res'' '''142''', 152-l 59;Segal, M. Dudai, Y. Amsterdam, A. (1978) Distribution of cu-bungarotoxin-<br />
binding cholinergic nicotinic receptor in rat brain. ''Brain Res'' '''148''', 105-l 19.</ref>.<br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1061532Sandbox 1742010-03-26T21:10:11Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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. 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> 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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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, 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.<br />
<br />
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>.<br />
<br />
<scene name='Sandbox_174/Domain_b/3'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/3'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<ref name="main"></ref>. The three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<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>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref> Tu, A.T. and Hong, B.S (1971) ''J Biol Chem''. '''246''', 2772-2779;Yang, C.C. ''Toxicon'' '''12''', 1-43.</ref> and strong acids<ref>Chiceportiche, R. Rochat, C. Sampien, F. Lazdunski, M. (1972) ''Biochemistry'' '''14''', 2081-2091;Chen, Y.H. Tai, J.C. Huand, W.J. Lau, M.Z. Hung, M.C. Lai, M.D. Yang, J.T. (1982) ''Biochemistry'' '''21''' 2592-2600</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<ref name="main">Love. A.R (FINISH)</ref>. <br />
==neuromuscular acetylcholine receptor binding==<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>Freedman, R. Wetmore, C. Stromberg, I. Leonard, S. Olsona, L. (1993) Alpha-Bungarotoxin Binding to Hippocampal Interneurons: lmmunocytochemical Characterization and Effects on Growth Factor Expression. ''Journal of Neuroscience'' 13:1965-1975. </ref>, which are mediated by two major classes of receptors: Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref> Miner and Collin, 1989;Luntz-Leybman et al. 1992 </ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref> Hunt and Schmidt, 1978;Segal et al.,1978;Clarke et al. 1985 </ref>.<br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1061517Sandbox 1742010-03-26T20:58:40Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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. 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> 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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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. 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.<br />
<br />
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. Stroud, R.M. (FINISH)</ref>.<br />
<br />
<scene name='Sandbox_174/Domain_b/3'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/3'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<ref name="main">Love, A.R (FINISH)</ref>. The three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<ref name="main">Love, A.R (FINISH)</ref>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref> Tu et al. 1971;Yang et al. 1975)</ref> and strong acids<ref>Chiceportiche et al.1972;Chen et al. 1982)</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<ref name="main">Love. A.R (FINISH)</ref>. <br />
==neuromuscular acetylcholine receptor binding==<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>Freedman, R. Wetmore, C. Stromberg, I. Leonard, S. Olsona, L. (1993) Alpha-Bungarotoxin Binding to Hippocampal Interneurons: lmmunocytochemical Characterization and Effects on Growth Factor Expression. ''Journal of Neuroscience'' 13:1965-1975. </ref>, which are mediated by two major classes of receptors: Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref> Miner and Collin, 1989;Luntz-Leybman et al. 1992 </ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref> Hunt and Schmidt, 1978;Segal et al.,1978;Clarke et al. 1985 </ref>.<br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1061515Sandbox 1742010-03-26T20:57:39Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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. 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.<br />
<br />
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. Stroud, R.M. (FINISH)</ref>.<br />
<br />
<scene name='Sandbox_174/Domain_b/3'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/3'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<ref name="main">Love, A.R (FINISH)</ref>. The three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<ref name="main">Love, A.R (FINISH)</ref>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref> Tu et al. 1971;Yang et al. 1975)</ref> and strong acids<ref>Chiceportiche et al.1972;Chen et al. 1982)</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<ref name="main">Love. A.R (FINISH)</ref>. <br />
==neuromuscular acetylcholine receptor binding==<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>Freedman, R. Wetmore, C. Stromberg, I. Leonard, S. Olsona, L. (1993) Alpha-Bungarotoxin Binding to Hippocampal Interneurons: lmmunocytochemical Characterization and Effects on Growth Factor Expression. ''Journal of Neuroscience'' 13:1965-1975. </ref>, which are mediated by two major classes of receptors: Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref> Miner and Collin, 1989;Luntz-Leybman et al. 1992 </ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref> Hunt and Schmidt, 1978;Segal et al.,1978;Clarke et al. 1985 </ref>.<br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1061512Sandbox 1742010-03-26T20:54:13Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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.<br />
<br />
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 (FINISH)</ref>.<br />
<br />
<scene name='Sandbox_174/Domain_b/3'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/3'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<ref name="main">Love, A.R (FINISH)</ref>. The three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<ref name="main">Love, A.R (FINISH)</ref>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref> Tu et al. 1971;Yang et al. 1975)</ref> and strong acids<ref>Chiceportiche et al.1972;Chen et al. 1982)</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<ref name="main">Love. A.R (FINISH)</ref>. <br />
==neuromuscular acetylcholine receptor binding==<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>Freedman, R. Wetmore, C. Stromberg, I. Leonard, S. Olsona, L. (1993) Alpha-Bungarotoxin Binding to Hippocampal Interneurons: lmmunocytochemical Characterization and Effects on Growth Factor Expression. ''Journal of Neuroscience'' 13:1965-1975. </ref>, which are mediated by two major classes of receptors: Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref> Miner and Collin, 1989;Luntz-Leybman et al. 1992 </ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref> Hunt and Schmidt, 1978;Segal et al.,1978;Clarke et al. 1985 </ref>.<br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1061505Sandbox 1742010-03-26T20:46:28Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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.<br />
<br />
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 (FINISH)</ref>.<br />
<br />
<scene name='Sandbox_174/Domain_b/3'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/3'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<ref name="main">Love, A.R (FINISH)</ref>. The three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<ref name="main">Love, A.R (FINISH)</ref>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref> Tu et al. 1971;Yang et al. 1975)</ref> and strong acids<ref>Chiceportiche et al.1972;Chen et al. 1982)</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<ref name="main">Love. A.R (FINISH)</ref>. <br />
==neuromuscular acetylcholine receptor binding==<br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>a-Bungarotoxin Binding to Hippocampal Interneurons:<br />
lmmunocytochemical Characterization and Effects on Growth Factor Expression</ref>, which are mediated by two major classes of receptors. Ganglionic type, and neuromuscular type, which pharmacological analysis of seizure genesis and habituation in the rat brain is thought to be mediated by the latter type <ref> Miner and Collin, 1989;Luntz-Leybman et al. 1992 </ref>. α-BGT demonstrates this relationship due to its prominent binding in the CA3 region of the hippocampus <ref> Hunt and Schmidt, 1978;Segal et al.,1978;Clarke et al. 1985 </ref><br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1060917Sandbox 1742010-03-25T21:04:29Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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.<br />
<br />
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 (FINISH)</ref>.<br />
<br />
<scene name='Sandbox_174/Domain_b/3'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/3'>Domain B</scene><br />
<br />
<br />
==Secondary structure & Disulphide bonds==<br />
Hydrogen bods present allow for an antiparallel β-sheet, which is the only secondary structure present and acts to keep the second and third loops roughly parallel<ref name="main">Love, A.R (FINISH)</ref>. The three-loop structure is preserved by four invariant disulphide bridges, which are present in all neurotoxins. The fifth disulphide bridge is located at the end of the second loop, and can be reduced without any effect on the binding affinity of the molecule, while a total loss of toxicity is demonstrated when the remaining disulphides are reduced, producing a random coil structure much different than the native conformation<ref name="main">Love, A.R (FINISH)</ref>. <br />
<br />
The comination of the multiple disulphide bonds and small amount of secondary structure is the cause for the extreme stability of neurotoxins like α-BGT, providing resistance to denaturing forces such as boiling<ref> Tu et al. 1971;Yang et al. 1975)</ref> and strong acids<ref>Chiceportiche et al.1972;Chen et al. 1982)</ref>. Functionally important residues contained in the extended loops are preserved by the clustering of disulphides near one end of the α-BGT molecule. This is due to an increased amount of flexibility in these extended loops, which is possibly quite important for interaction with acetylcholine receptors.<br />
<br />
=Functions=<br />
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<ref name="main">Love. A.R (FINISH)</ref>. <br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>a-Bungarotoxin Binding to Hippocampal Interneurons:<br />
lmmunocytochemical Characterization and Effects on Growth Factor<br />
Expression</ref>. Second note to refd<ref>article 2 </ref><br />
<br />
<br />
Seizure genesisa nd habituation of responseto sensorys timuli have been linked to nicotinic mechanisms (Marks et al., 1989;<br />
Luntz-Leybman et al., 1992). These functions are closely associated<br />
with the CA3 field (Schwartzkroin, 1986; Bickford-<br />
Wimer et al., 1990). Nicotinic responsesa re mediated by two<br />
major classeso f receptors, ganglionic type and neuromuscular<br />
type. Pharmacological analysis of both seizure genesis and habituation<br />
in rat brain implicates mediation by a neuromuscular<br />
type (Miner and Collins, 1989; Luntz-Leybman et al., 1992).<br />
These data are supported by the prominent binding of the neuromuscular-<br />
type antagonist oc-bungarotoxin (a-BT) in the CA3<br />
field of the hippocampus (Hunt and Schmidt, 1978; Segal et al.,<br />
1978; Clarke et al., 1985<br />
<br />
==neuromuscular acetylcholine receptor binding==<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1060905Sandbox 1742010-03-25T20:29:57Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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.<br />
<scene name='Sandbox_174/Domain_b/3'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/3'>Domain B</scene><br />
<br />
<br />
==Active sites & ==<br />
<br />
=Functions=<br />
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<ref name="main">Love. A.R (FINISH)</ref>. <br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>a-Bungarotoxin Binding to Hippocampal Interneurons:<br />
lmmunocytochemical Characterization and Effects on Growth Factor<br />
Expression</ref>. Second note to refd<ref>article 2 </ref><br />
<br />
<br />
Seizure genesisa nd habituation of responseto sensorys timuli have been linked to nicotinic mechanisms (Marks et al., 1989;<br />
Luntz-Leybman et al., 1992). These functions are closely associated<br />
with the CA3 field (Schwartzkroin, 1986; Bickford-<br />
Wimer et al., 1990). Nicotinic responsesa re mediated by two<br />
major classeso f receptors, ganglionic type and neuromuscular<br />
type. Pharmacological analysis of both seizure genesis and habituation<br />
in rat brain implicates mediation by a neuromuscular<br />
type (Miner and Collins, 1989; Luntz-Leybman et al., 1992).<br />
These data are supported by the prominent binding of the neuromuscular-<br />
type antagonist oc-bungarotoxin (a-BT) in the CA3<br />
field of the hippocampus (Hunt and Schmidt, 1978; Segal et al.,<br />
1978; Clarke et al., 1985<br />
<br />
==neuromuscular acetylcholine receptor binding==<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1060901Sandbox 1742010-03-25T20:22:25Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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.<br />
<scene name='Sandbox_174/Domain_b/1'>Domain A</scene><br />
<scene name='Sandbox_174/Domain_a/1'>Domain B</scene><br />
<br />
<br />
==Active sites & ==<br />
<br />
=Functions=<br />
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<ref name="main">Love. A.R (FINISH)</ref>. <br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>a-Bungarotoxin Binding to Hippocampal Interneurons:<br />
lmmunocytochemical Characterization and Effects on Growth Factor<br />
Expression</ref>. Second note to refd<ref>article 2 </ref><br />
<br />
<br />
Seizure genesisa nd habituation of responseto sensorys timuli have been linked to nicotinic mechanisms (Marks et al., 1989;<br />
Luntz-Leybman et al., 1992). These functions are closely associated<br />
with the CA3 field (Schwartzkroin, 1986; Bickford-<br />
Wimer et al., 1990). Nicotinic responsesa re mediated by two<br />
major classeso f receptors, ganglionic type and neuromuscular<br />
type. Pharmacological analysis of both seizure genesis and habituation<br />
in rat brain implicates mediation by a neuromuscular<br />
type (Miner and Collins, 1989; Luntz-Leybman et al., 1992).<br />
These data are supported by the prominent binding of the neuromuscular-<br />
type antagonist oc-bungarotoxin (a-BT) in the CA3<br />
field of the hippocampus (Hunt and Schmidt, 1978; Segal et al.,<br />
1978; Clarke et al., 1985<br />
<br />
==neuromuscular acetylcholine receptor binding==<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1060900Sandbox 1742010-03-25T20:20:31Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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.<br />
<scene name='Sandbox_174/Domain_b/1'>Domain B</scene><br />
Domain B<br />
<br />
<br />
==Active sites & ==<br />
<br />
=Functions=<br />
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<ref name="main">Love. A.R (FINISH)</ref>. <br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>a-Bungarotoxin Binding to Hippocampal Interneurons:<br />
lmmunocytochemical Characterization and Effects on Growth Factor<br />
Expression</ref>. Second note to refd<ref>article 2 </ref><br />
<br />
<br />
Seizure genesisa nd habituation of responseto sensorys timuli have been linked to nicotinic mechanisms (Marks et al., 1989;<br />
Luntz-Leybman et al., 1992). These functions are closely associated<br />
with the CA3 field (Schwartzkroin, 1986; Bickford-<br />
Wimer et al., 1990). Nicotinic responsesa re mediated by two<br />
major classeso f receptors, ganglionic type and neuromuscular<br />
type. Pharmacological analysis of both seizure genesis and habituation<br />
in rat brain implicates mediation by a neuromuscular<br />
type (Miner and Collins, 1989; Luntz-Leybman et al., 1992).<br />
These data are supported by the prominent binding of the neuromuscular-<br />
type antagonist oc-bungarotoxin (a-BT) in the CA3<br />
field of the hippocampus (Hunt and Schmidt, 1978; Segal et al.,<br />
1978; Clarke et al., 1985<br />
<br />
==neuromuscular acetylcholine receptor binding==<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1060899Sandbox 1742010-03-25T20:19:10Z<p>Simon Loewen: </p>
<hr />
<div>{{STRUCTURE_2abx | PDB=2abx | SCENE= }}<br />
=Alpha-Bungarotoxin=<br />
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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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.<br />
<scene name='Sandbox_174/Domain B/1'>Domain B</scene><br />
Domain B<br />
<br />
<br />
==Active sites & ==<br />
<br />
=Functions=<br />
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<ref name="main">Love. A.R (FINISH)</ref>. <br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>a-Bungarotoxin Binding to Hippocampal Interneurons:<br />
lmmunocytochemical Characterization and Effects on Growth Factor<br />
Expression</ref>. Second note to refd<ref>article 2 </ref><br />
<br />
<br />
Seizure genesisa nd habituation of responseto sensorys timuli have been linked to nicotinic mechanisms (Marks et al., 1989;<br />
Luntz-Leybman et al., 1992). These functions are closely associated<br />
with the CA3 field (Schwartzkroin, 1986; Bickford-<br />
Wimer et al., 1990). Nicotinic responsesa re mediated by two<br />
major classeso f receptors, ganglionic type and neuromuscular<br />
type. Pharmacological analysis of both seizure genesis and habituation<br />
in rat brain implicates mediation by a neuromuscular<br />
type (Miner and Collins, 1989; Luntz-Leybman et al., 1992).<br />
These data are supported by the prominent binding of the neuromuscular-<br />
type antagonist oc-bungarotoxin (a-BT) in the CA3<br />
field of the hippocampus (Hunt and Schmidt, 1978; Segal et al.,<br />
1978; Clarke et al., 1985<br />
<br />
==neuromuscular acetylcholine receptor binding==<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1060887Sandbox 1742010-03-25T19:58:41Z<p>Simon Loewen: </p>
<hr />
<div><applet load='2abx' size='300' frame='true' align='right' /><br />
<br />
=Alpha-Bungarotoxin=<br />
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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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.<br />
<br />
<br />
==Active sites & ==<br />
<br />
=Functions=<br />
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<ref name="main">Love. A.R (FINISH)</ref>. <br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>a-Bungarotoxin Binding to Hippocampal Interneurons:<br />
lmmunocytochemical Characterization and Effects on Growth Factor<br />
Expression</ref>. Second note to refd<ref>article 2 </ref><br />
<br />
<br />
Seizure genesisa nd habituation of responseto sensorys timuli have been linked to nicotinic mechanisms (Marks et al., 1989;<br />
Luntz-Leybman et al., 1992). These functions are closely associated<br />
with the CA3 field (Schwartzkroin, 1986; Bickford-<br />
Wimer et al., 1990). Nicotinic responsesa re mediated by two<br />
major classeso f receptors, ganglionic type and neuromuscular<br />
type. Pharmacological analysis of both seizure genesis and habituation<br />
in rat brain implicates mediation by a neuromuscular<br />
type (Miner and Collins, 1989; Luntz-Leybman et al., 1992).<br />
These data are supported by the prominent binding of the neuromuscular-<br />
type antagonist oc-bungarotoxin (a-BT) in the CA3<br />
field of the hippocampus (Hunt and Schmidt, 1978; Segal et al.,<br />
1978; Clarke et al., 1985<br />
<br />
==neuromuscular acetylcholine receptor binding==<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1060884Sandbox 1742010-03-25T19:42:18Z<p>Simon Loewen: </p>
<hr />
<div><applet load='2abx' size='300' frame='true' align='right' /><br />
<br />
=Alpha-Bungarotoxin=<br />
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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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 <scene name='Sandbox_174/Disulphides/2'>Disulphide Bonds</scene><br />
<br />
<br />
==Active sites & ==<br />
<br />
=Functions=<br />
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<ref name="main">Love. A.R (FINISH)</ref>. <br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>a-Bungarotoxin Binding to Hippocampal Interneurons:<br />
lmmunocytochemical Characterization and Effects on Growth Factor<br />
Expression</ref>. Second note to refd<ref>article 2 </ref><br />
<br />
<br />
Seizure genesisa nd habituation of responseto sensorys timuli have been linked to nicotinic mechanisms (Marks et al., 1989;<br />
Luntz-Leybman et al., 1992). These functions are closely associated<br />
with the CA3 field (Schwartzkroin, 1986; Bickford-<br />
Wimer et al., 1990). Nicotinic responsesa re mediated by two<br />
major classeso f receptors, ganglionic type and neuromuscular<br />
type. Pharmacological analysis of both seizure genesis and habituation<br />
in rat brain implicates mediation by a neuromuscular<br />
type (Miner and Collins, 1989; Luntz-Leybman et al., 1992).<br />
These data are supported by the prominent binding of the neuromuscular-<br />
type antagonist oc-bungarotoxin (a-BT) in the CA3<br />
field of the hippocampus (Hunt and Schmidt, 1978; Segal et al.,<br />
1978; Clarke et al., 1985<br />
<br />
==neuromuscular acetylcholine receptor binding==<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1060883Sandbox 1742010-03-25T19:38:11Z<p>Simon Loewen: </p>
<hr />
<div><applet load='2abx' size='300' frame='true' align='right' /><br />
<br />
=Alpha-Bungarotoxin=<br />
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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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 <scene name='Sandbox_174/Disulphides/1'>Disulphide Bonds</scene><br />
<br />
<br />
==Active sites & ==<br />
<br />
=Functions=<br />
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<ref name="main">Love. A.R (FINISH)</ref>. <br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>a-Bungarotoxin Binding to Hippocampal Interneurons:<br />
lmmunocytochemical Characterization and Effects on Growth Factor<br />
Expression</ref>. Second note to refd<ref>article 2 </ref><br />
<br />
<br />
Seizure genesisa nd habituation of responseto sensorys timuli have been linked to nicotinic mechanisms (Marks et al., 1989;<br />
Luntz-Leybman et al., 1992). These functions are closely associated<br />
with the CA3 field (Schwartzkroin, 1986; Bickford-<br />
Wimer et al., 1990). Nicotinic responsesa re mediated by two<br />
major classeso f receptors, ganglionic type and neuromuscular<br />
type. Pharmacological analysis of both seizure genesis and habituation<br />
in rat brain implicates mediation by a neuromuscular<br />
type (Miner and Collins, 1989; Luntz-Leybman et al., 1992).<br />
These data are supported by the prominent binding of the neuromuscular-<br />
type antagonist oc-bungarotoxin (a-BT) in the CA3<br />
field of the hippocampus (Hunt and Schmidt, 1978; Segal et al.,<br />
1978; Clarke et al., 1985<br />
<br />
==neuromuscular acetylcholine receptor binding==<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewenhttps://proteopedia.org/index.php?title=Sandbox_174&diff=1060882Sandbox 1742010-03-25T19:37:03Z<p>Simon Loewen: </p>
<hr />
<div><applet load='2abx' size='300' frame='true' align='right' /><br />
<br />
=Alpha-Bungarotoxin=<br />
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.<br />
<br />
=General Structure=<br />
[[Image:alpha-bungarotoxin1.PNG]] <br />
<br />
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 <scene name='Sandbox_174/Disulphides/2'>Disulphide Bonds</scene><br />
<br />
<br />
==Active sites & ==<br />
<br />
=Functions=<br />
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<ref name="main">Love. A.R (FINISH)</ref>. <br />
==α7 nicotinic acetylcholine receptor binding==<br />
Reponse to sensory stimuli and seizure genesis has been linked to nicotinic mechanisms<ref>a-Bungarotoxin Binding to Hippocampal Interneurons:<br />
lmmunocytochemical Characterization and Effects on Growth Factor<br />
Expression</ref>. Second note to refd<ref>article 2 </ref><br />
<br />
<br />
Seizure genesisa nd habituation of responseto sensorys timuli have been linked to nicotinic mechanisms (Marks et al., 1989;<br />
Luntz-Leybman et al., 1992). These functions are closely associated<br />
with the CA3 field (Schwartzkroin, 1986; Bickford-<br />
Wimer et al., 1990). Nicotinic responsesa re mediated by two<br />
major classeso f receptors, ganglionic type and neuromuscular<br />
type. Pharmacological analysis of both seizure genesis and habituation<br />
in rat brain implicates mediation by a neuromuscular<br />
type (Miner and Collins, 1989; Luntz-Leybman et al., 1992).<br />
These data are supported by the prominent binding of the neuromuscular-<br />
type antagonist oc-bungarotoxin (a-BT) in the CA3<br />
field of the hippocampus (Hunt and Schmidt, 1978; Segal et al.,<br />
1978; Clarke et al., 1985<br />
<br />
==neuromuscular acetylcholine receptor binding==<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<scene name='Sandbox_174/Newscene/1'>All residues</scene><br />
<table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>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.[[User:Andrea Gorrell|Andrea Gorrell]].</td></tr></div>Simon Loewen