AChE bivalent inhibitors (Part II)
From Proteopedia
This page is a continuation of the page AChE bivalent inhibitors
|
Similarly to the other AChE bivalent inhibitors, BW284C51 (BW) also binds the TcAChE at its . At the CAS there is a cation-aromatic interaction between BW quaternary group and (colored orange), 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 (colored cyan) 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 (decamethonium, colored gray) and (Aricept, colored blueviolet) 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 (colored yellow). These interactions might be most important in the binding affinity of these 3 inhibitors. have a similar trajectory along the active-site gorge, while BW traces a different route, especially near the CAS at its bottom.
