Sandbox 250: Difference between revisions

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FAS-II binds to and inhibits AChE using two major mechanisms:
FAS-II binds to and inhibits AChE using two major mechanisms:


1. Amino acid specificity: residues <scene name='Sandbox_250/Ache_fas2/14'>Thr8, Arg27 and Met33</scene> are located on two of the three fingers of FAS-II. When FAS-II <scene name='Sandbox_250/Ache_fas2/17'>binds</scene> to AChE, Arg27 and Met33 interact with Trp279 part of the PAS, while Thr8 interact with Tyr70, also part of the PAS.
1. Long-range electrostatic complementarity: the positive lower region of FAS-II is attracted to the highly negative top region of AChE.  


2. Shape: Once bound to the PAS, two loops of FAS-II fit in to the AChE active-site gorge like a hand fits into a glove. Once this occurs, the entrance of the gorge is <scene name='Sandbox_250/Ache_fas2/13'>blocked</scene> such that acetylcholine may not enter, and therefore it will not be hydrolysed. This results in the increased levels of AChE in the cholinergic synapse, and ultimately death.
2. Amino acid specificity: residues <scene name='Sandbox_250/Ache_fas2/14'>Thr8, Arg27 and Met33</scene> are located on two of the three fingers of FAS-II. When FAS-II <scene name='Sandbox_250/Ache_fas2/17'>binds</scene> to AChE, Arg27 and Met33 interact with Trp279 part of the PAS, while Thr8 interact with Tyr70, also part of the PAS.
 
3. Shape: Once bound to the PAS, two loops of FAS-II fit in to the AChE active-site gorge like a hand fits into a glove. Once this occurs, the entrance of the gorge is <scene name='Sandbox_250/Ache_fas2/13'>blocked</scene> such that acetylcholine may not enter, and therefore it will not be hydrolysed. This results in the increased levels of AChE in the cholinergic synapse, and ultimately death.