Sandbox Reserved 932: Difference between revisions

Line 21:

Three-finger toxins (3FTXs) are the most common family of snake venom proteins; these venoms can be found in elapid, colubrid and hydrophiid snakes and include toxins such as α-cobratoxin and α-bungarotoxin. 3FTXs are non-enzymatic proteins which form a structurally conserved superfamily whose members all share a highly conserved structure. <ref name=Dufton></ref><ref name=Endo></ref>The core structure of 3FTXs is formed by three <scene name='57/579702/Three_fingers/1'>three β-stranded polypeptide loops</scene> joined together by four conserved disulphide bridges located in the <scene name='57/579702/3ftx_beta_strands/2'>core</scene> of the protein. Despite the similarities in the structure of different toxins belonging to the family, the 3FTXs from various venoms have a variety of receptors/acceptors and exhibit differential responses in their targets. The members of the family can vary slightly in: the length and type of twists of the tree loops; the length and type of turns of the N and C-terminal tail and the amount of β-sheets in the overall structure. These differences allow for the specificity and toxicity of the proteins to their targets. <ref name=Pawlak/>

Three-finger toxins (3FTXs) are the most common family of snake venom proteins; these venoms can be found in elapid, colubrid and hydrophiid snakes and include toxins such as α-cobratoxin and α-bungarotoxin. 3FTXs are non-enzymatic proteins which form a structurally conserved superfamily whose members all share a highly conserved structure. <ref name=Dufton></ref><ref name=Endo></ref>The core structure of 3FTXs is formed by three <scene name='57/579702/Three_fingers/1'>three β-stranded polypeptide loops</scene> joined together by four conserved disulphide bridges located in the <scene name='57/579702/3ftx_beta_strands/2'>core</scene> of the protein. Despite the similarities in the structure of different toxins belonging to the family, the 3FTXs from various venoms have a variety of receptors/acceptors and exhibit differential responses in their targets. The members of the family can vary slightly in: the length and type of twists of the tree loops; the length and type of turns of the N and C-terminal tail and the amount of β-sheets in the overall structure. These differences allow for the specificity and toxicity of the proteins to their targets. <ref name=Pawlak></ref>

Denmotoxin shares approximately 30% sequence similarity with other 3FTXs with an exception of exhibiting approximately 50% sequence similarity with another colubrid snake venom α-colubritoxin. Despite the relatively low sequence similarity, denmotoxin possesses all the residues needed to maintain the 3 finger fold. A large part of the sequence similarity between denmotoxin and other 3FTXs is due to the highly conserved disulphides and a number of structurally important residues. <ref name=Pawlak/>

Line 45:

Biochemistry of denmotoxin is unique for its taxon specificity to bird nicotinic acetylcholine receptors (nAChR). Binding of denmotoxin to chick muscle AChR (α1βγδ) is a highly irreversible whereas interaction with identical subunit assembly in mouse AChR is reversible. The reversible binding allows the receptor to function properly, but in the case of irreversible binding nAChR is prevented of natural agonist activation. Previous studies <ref>Samson. A. O. & Levitt M., [http://pubs.acs.org/doi/abs/10.1021/bi702272j "Inhibition Mechanism of the Acetylcholine Receptor by α-Neurotoxins as Revealed by Normal-Mode Dynamics"], ''Biochemistry, 2008, 47 (13), pp 4065–4070'', March 8, 2008. Retrieved May 19, 2014.</ref> with 3FTXs have shown that the binding of toxin leads to “locking down” of the nACh receptor, preventing required conformational change for ion channel activation and induction of signal. <ref name=Pawlak/>

There are no significant differences in the sequence of functionally important loops A-F of nAChR in mice and chicks. However in the prior region of loop F, chicks have several changes in their amino acid composition leading to introduction of positive charge spatially in the front of the functionally active loop F. This might have important functionality in the attraction and binding of denmotoxin specifically to bird nAChRs. However, no crystal structure of denmotoxin binding to nAChR has been resolved; thus denmotoxin could also utilise a yet uncharacterised binding site in the receptor <ref name=Pawlak/>

There are no significant differences in the sequence of functionally important loops A-F of nAChR in mice and chicks. However in the prior region of loop F, chicks have several changes in their amino acid composition leading to introduction of positive charge spatially in the front of the functionally active loop F. This might have important functionality in the attraction and binding of denmotoxin specifically to bird nAChRs. However, no crystal structure of denmotoxin binding to nAChR has been resolved; thus denmotoxin could also utilise a yet uncharacterised binding site in the receptor. <ref name=Pawlak/>

Sandbox Reserved 932: Difference between revisions

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 21: / Line 21: @@
-Three-finger toxins (3FTXs) are the most common family of snake venom proteins; these venoms can be found in elapid, colubrid and hydrophiid snakes and include toxins such as α-cobratoxin and α-bungarotoxin. 3FTXs are  non-enzymatic proteins which form a structurally conserved superfamily whose members all share a highly conserved structure. <ref name=Dufton></ref><ref name=Endo></ref>The core structure of 3FTXs is formed by three <scene name='57/579702/Three_fingers/1'>three β-stranded polypeptide loops</scene> joined together by four conserved disulphide bridges located in the <scene name='57/579702/3ftx_beta_strands/2'>core</scene> of the protein. Despite the similarities in the structure of different toxins belonging to the family, the 3FTXs from various venoms have a variety of receptors/acceptors and exhibit differential responses in their targets. The members of the family can vary slightly in: the length and type of twists of the tree loops; the length and type of turns of the N and C-terminal tail and the amount of β-sheets in the overall structure. These differences allow for the specificity and toxicity of the proteins to their targets. <ref name=Pawlak/>
+Three-finger toxins (3FTXs) are the most common family of snake venom proteins; these venoms can be found in elapid, colubrid and hydrophiid snakes and include toxins such as α-cobratoxin and α-bungarotoxin. 3FTXs are  non-enzymatic proteins which form a structurally conserved superfamily whose members all share a highly conserved structure. <ref name=Dufton></ref><ref name=Endo></ref>The core structure of 3FTXs is formed by three <scene name='57/579702/Three_fingers/1'>three β-stranded polypeptide loops</scene> joined together by four conserved disulphide bridges located in the <scene name='57/579702/3ftx_beta_strands/2'>core</scene> of the protein. Despite the similarities in the structure of different toxins belonging to the family, the 3FTXs from various venoms have a variety of receptors/acceptors and exhibit differential responses in their targets. The members of the family can vary slightly in: the length and type of twists of the tree loops; the length and type of turns of the N and C-terminal tail and the amount of β-sheets in the overall structure. These differences allow for the specificity and toxicity of the proteins to their targets. <ref name=Pawlak></ref>
 Denmotoxin shares approximately 30% sequence similarity with other 3FTXs with an exception of exhibiting approximately 50% sequence similarity with another colubrid snake venom α-colubritoxin. Despite the relatively low sequence similarity, denmotoxin possesses all the residues needed to maintain the 3 finger fold. A large part of the sequence similarity between denmotoxin and other 3FTXs is due to the highly conserved disulphides and a number of structurally important residues. <ref name=Pawlak/>
@@ Line 45: / Line 45: @@
 Biochemistry of denmotoxin is unique for its taxon specificity to bird nicotinic acetylcholine receptors (nAChR). Binding of denmotoxin to chick muscle AChR (α1βγδ) is a highly irreversible whereas interaction with identical subunit assembly in mouse AChR is reversible. The reversible binding allows the receptor to function properly, but in the case of irreversible binding nAChR is prevented of natural agonist activation. Previous studies <ref>Samson. A. O. & Levitt M., [http://pubs.acs.org/doi/abs/10.1021/bi702272j "Inhibition Mechanism of the Acetylcholine Receptor by α-Neurotoxins as Revealed by Normal-Mode Dynamics"], ''Biochemistry, 2008, 47 (13), pp 4065–4070'', March 8, 2008. Retrieved May 19, 2014.</ref> with 3FTXs have shown that the binding of toxin leads to “locking down” of the nACh receptor, preventing required conformational change for ion channel activation and induction of signal. <ref name=Pawlak/>
-There are no significant differences in the sequence of functionally important loops A-F of nAChR in mice and chicks. However in the prior region of loop F, chicks have several changes in their amino acid composition leading to introduction of positive charge spatially in the front of the functionally active loop F. This might have important functionality in the attraction and binding of denmotoxin specifically to bird nAChRs. However, no crystal structure of denmotoxin binding to nAChR has been resolved; thus denmotoxin could also utilise a yet uncharacterised binding site in the receptor  <ref name=Pawlak/>
+There are no significant differences in the sequence of functionally important loops A-F of nAChR in mice and chicks. However in the prior region of loop F, chicks have several changes in their amino acid composition leading to introduction of positive charge spatially in the front of the functionally active loop F. This might have important functionality in the attraction and binding of denmotoxin specifically to bird nAChRs. However, no crystal structure of denmotoxin binding to nAChR has been resolved; thus denmotoxin could also utilise a yet uncharacterised binding site in the receptor. <ref name=Pawlak/>