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| + | #REDIRECT [[AChE inhibitors and substrates]] |
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| - | <applet load='ACHE3.pdb' size='500' frame='true' align='right'
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| - | scene='1e3q/Cv/1' />
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| - | Similarly to the other AChE bivalent inhibitors, <font color='magenta'><b>BW284C51 (BW)</b></font> also binds the ''Tc''AChE at its <scene name='1e3q/Active_site/1'>active site</scene>. At the CAS there is a cation-aromatic interaction between BW quaternary group and <scene name='1e3q/Active_site/2'>Trp84</scene> <font color='orange'><b>(colored orange)</b></font>, an aromatic-aromatic interaction between BW and His440, and an electrostatic interaction between the proximal quaternary group and Glu199. Near the PAS the distal quaternary group of BW makes a quaternary interaction with <scene name='1e3q/Active_site/3'>Trp279</scene> <font color='cyan'><b>(colored cyan)</b></font> and an aromatic interaction with Tyr334. In the middle of the active-site gorge there is a hydrogen bond of 3.53 Å between the BW carbonyl and Tyr121 OH, as well as alkyl interactions with Phe331. The superposition of BW with other AChE bivalent inhibitors <scene name='1e3q/Active_site/4'>DECA</scene> <font color='gray'><b>(decamethonium, colored gray)</b></font> and <scene name='1e3q/Active_site/5'>E2020</scene> <font color='blueviolet'><b>(Aricept, colored blueviolet)</b></font> within the active-site gorge of TcAChE reveals similar interactions in their mode of binding. All these 3 inhibitors form cation-π and π-π interactions with active-site gorge aromatic residues <scene name='1e3q/Active_site/6'>(Tyr70, Trp84, Trp279 and Phe330 or Tyr334)</scene> <font color='yellow'><b>(colored yellow)</b></font>. These interactions might be most important in the binding affinity of these 3 inhibitors. <scene name='1e3q/Active_site/7'>DECA and E2020</scene> have a similar trajectory along the active-site gorge, while BW traces a different route, especially near the CAS at its bottom.
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Current revision
- REDIRECT AChE inhibitors and substrates
