Sandbox Reserved 932: Difference between revisions

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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; denmotoxin could also ~~use another~~ 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/>

===Conclusions===

3FTXs are the most abundant and well characterized snake venom protein family. The broad spectrum of 3FTX targets, including nAChRs, phospholipids and L-type calcium channels, make the proteins interesting for research. The interaction of ~~the~~ 3FTX with their targets result in a myriad of pharmacological effects. Understanding how the architecture of the proteins of the family result in the varying ~~mechanism actions~~ can prove a valuable tool for rational drug design.

3FTXs are the most abundant and well characterized snake venom protein family. The broad spectrum of 3FTX targets, including nAChRs, phospholipids and L-type calcium channels, make the proteins interesting for research. The interaction of 3FTX-proteins with their targets result in a myriad of pharmacological effects. Study of the 3FTX family proteins can also be utilised in the research of their receptors. Understanding how the architecture of the proteins of the family result in the varying mechanisms of action can prove a valuable tool for rational drug design.

Whilst the highly conserved three finger structural motif is present in denmotoxin minor structural differences can be found when compared to other proteins of family. These differences are responsible for the recognition of target receptors and can modulate both the specificity and toxicity of the venom.

Whilst the highly conserved three finger structural motif is present in denmotoxin minor structural differences can be found when compared to other proteins of the family. These differences are responsible for the recognition of target receptors and can modulate both the specificity and toxicity of the venom.

Sandbox Reserved 932: Difference between revisions

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@@ 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; denmotoxin could also use another 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/>
 ===Conclusions===
-FTXs are the most abundant and well characterized snake venom protein family. The broad spectrum of 3FTX targets, including nAChRs, phospholipids and L-type calcium channels, make the proteins interesting for research. The interaction of the 3FTX with their targets result in a myriad of pharmacological effects. Understanding how the architecture of the proteins of the family result in the varying mechanism actions can prove a valuable tool for rational drug design.
+FTXs are the most abundant and well characterized snake venom protein family. The broad spectrum of 3FTX targets, including nAChRs, phospholipids and L-type calcium channels, make the proteins interesting for research. The interaction of  3FTX-proteins with their targets result in a myriad of pharmacological effects. Study of the 3FTX family proteins can also be utilised in the research of their receptors. Understanding how the architecture of the proteins of the family result in the varying mechanisms of action can prove a valuable tool for rational drug design.
-Whilst the highly conserved three finger structural motif is present in denmotoxin minor structural differences can be found when compared to other proteins of family. These differences are responsible for the recognition of target receptors and can modulate both the specificity and toxicity of the venom.
+Whilst the highly conserved three finger structural motif is present in denmotoxin minor structural differences can be found when compared to other proteins of the family. These differences are responsible for the recognition of target receptors and can modulate both the specificity and toxicity of the venom.