Sandbox Reserved 932: Difference between revisions
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[[Image:Bungarotoxin interaction with nACHr figure text.png|300px|right|thumb| Figure 3. Suggested interaction of '''α-bungarotoxin''' in binding pocket of nAChR (simplified figure) [PDB=4HQP]]] | [[Image:Bungarotoxin interaction with nACHr figure text.png|300px|right|thumb| Figure 3. Suggested interaction of '''α-bungarotoxin''' in binding pocket of nAChR (simplified figure) [PDB=4HQP]]] | ||
Most of the 3FTX family proteins possess a highly conserved arginine in the tip of their binding loop responsible for interaction with nAChRs. This interaction was determined by resolving a structure of α7 nAChR chimera in a complex with α-bungarotoxin (fig. 3) <ref>Huang S. ''et al.'', [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920732/ "Complex between α-bungarotoxin and an α7 nicotinic receptor ligand-binding domain chimaera"], ''Biochem J. 454(2): 303–310.'', Septemper 1, 2013. Retrieved May 19, 2014.</ref>. In denmotoxin, this loop contains | Most of the 3FTX family proteins possess a highly conserved arginine in the tip of their binding loop responsible for interaction with nAChRs. This interaction was determined by resolving a structure of α7 nAChR chimera in a complex with α-bungarotoxin (fig. 3) <ref>Huang S. ''et al.'', [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920732/ "Complex between α-bungarotoxin and an α7 nicotinic receptor ligand-binding domain chimaera"], ''Biochem J. 454(2): 303–310.'', Septemper 1, 2013. Retrieved May 19, 2014.</ref>. In denmotoxin, this loop contains several changes in its sequence; arginine has replaced by aspartic acid (ASP41) and two additional glutamates (GLU42 & GLU45) generate untypical <scene name='57/579702/Active_site/2'>negative charge</scene> into the loop. <ref name=Pawlak/> | ||
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/> | 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/> | ||
