Aricept Complexed with Acetylcholinesterase: Difference between revisions

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OCA, Joel L. Sussman, Eran Hodis, Wayne Decatur, Jaime Prilusky, Alexander Berchansky, David Canner, Lucie Kolarova, Pham Ngoc Phuong, Angel Herraez, Michal Harel

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 ==Results==
-The X-ray structure of the E2020-''Tc''AChE complex shows that E2020 has a <scene name='1eve/E2020_close_up_with_84_279/3'>unique orientation</scene>, along the active-site gorge, extending from the anionic subsite (<scene name='1eve/E2020_close_up_with_84lbld/1'>W84</scene>) of the, active site, at the bottom, to the peripheral anionic site (<scene name='1eve/E2020_close_up_with_84_279lbld/1'>near W279</scene>), at the top, via aromatic stacking interactions with conserved aromatic acid residues. E2020 does not, however, interact directly with either the catalytic triad, or the 'oxyanion hole', but only indirectly via solvent molecules., CONCLUSIONS: The X-ray struture shows, a posteriori, that the design of E2020 took, advantage of several important features of the active-site gorge of AChE, to produce a drug with both high affinity for AChE and a high degree of, selectivity for AChE versus butyrylcholinesterase (BChE). It also, delineates voids within the gorge that are not occupied by E2020 and could, provide sites for potential modification of E2020 to produce drugs with, improved pharmacological profiles.
+The X-ray structure of the E2020-''Tc''AChE complex shows that E2020 has a <scene name='1eve/E2020_close_up_with_84_279/3'>unique orientation</scene>, along the active-site gorge, extending from the anionic subsite (<scene name='1eve/E2020_close_up_with_84lbld/1'>W84</scene>) of the, active site, at the bottom, to the peripheral anionic site (<scene name='1eve/E2020_close_up_with_84_279lbld/1'>near W279</scene>), at the top, via aromatic stacking interactions with conserved aromatic acid residues. E2020 does not, however, interact directly with either the catalytic triad, or the 'oxyanion hole', but only indirectly via solvent molecules.
+==Conclusions==
+The X-ray struture shows, a posteriori, that the design of E2020 took, advantage of several important features of the active-site gorge of AChE, to produce a drug with both high affinity for AChE and a high degree of, selectivity for AChE versus butyrylcholinesterase (BChE). It also, delineates voids within the gorge that are not occupied by E2020 and could, provide sites for potential modification of E2020 to produce drugs with, improved pharmacological profiles.
 ==About this Structure==