Sandbox E20
From Proteopedia
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==Results== | ==Results== | ||
| - | The X-ray structure of the E2020-''Tc''AChE complex shows that E2020 has a <scene name='1eve/E2020_close_up_with_84_279/13'>unique orientation</scene> along the active-site gorge, extending from the anionic subsite (<scene name=' | + | The X-ray structure of the E2020-''Tc''AChE complex shows that E2020 has a <scene name='1eve/E2020_close_up_with_84_279/13'>unique orientation</scene> along the active-site gorge, extending from the anionic subsite (<scene name='1eve/E2020_close_up_with_84lbld/7'>W84</scene>) of the active site, at the bottom, to the peripheral anionic site (<scene name='1eve/E2020_close_up_with_84_279lbld/5'>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 <scene name='1eve/E20_interactionshown/8'>indirectly via solvent molecules</scene>. |
==Conclusions== | ==Conclusions== | ||
The X-ray structure 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 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. | ||
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| + | <scene name='90/902074/Cartoon_and_e20/1'>cartoon_and_E2020</scene> | ||
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| + | <jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenUnChecked>hide E20 or hidden | ||
| + | </scriptWhenUnChecked> | ||
| + | <scriptWhenchecked>hide hidden and not (E20) | ||
| + | </scriptWhenchecked> | ||
| + | <checked>true</checked> | ||
| + | <text>ligand</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol> | ||
| + | |||
| + | <scene name='90/902074/T/1'>residues near E2020</scene> | ||
==About this Structure== | ==About this Structure== | ||
Current revision
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Reference
Structure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti-Alzheimer drugs., Kryger G, Silman I, Sussman JL, Structure. 1999 Mar 15;7(3):297-307. PMID:10368299
