Kryger_1998_J.Physiol.Paris_92_191

Reference

Title : Three-dimensional structure of a complex of E2020 with acetylcholinesterase from Torpedo californica - Kryger_1998_J.Physiol.Paris_92_191
Author(s) : Kryger G , Silman I , Sussman JL
Ref : Journal de Physiologie Paris , 92 :191 , 1998
Abstract : The 3D structure of a complex of the anti-Alzheimer drug, E2020, also known as Aricept, with Torpedo californica acetylcholinesterase is reported. The X-ray structure, at 2.5 A resolution, shows that the elongated E2020 molecule spans the entire length of the active-site gorge of the enzyme. It thus interacts with both the 'anionic' subsite, at the bottom of the gorge, and with the peripheral anionic site, near its entrance, via aromatic stacking interactions with conserved aromatic residues. It does not interact directly with either the catalytic triad or with the 'oxyanion hole'. Although E2020 is a chiral molecule, and both the S and R enantiomers have similar affinity for the enzyme, only the R enantiomer is bound within the active-site gorge when the racemate is soaked into the crystal. The selectivity of E2020 for acetylcholinesterase, relative to butyrylcholinesterase, can be ascribed primarily to its interactions with Trp279 and Phe330, which are absent in the latter.
ESTHER : Kryger_1998_J.Physiol.Paris_92_191
PubMedSearch : Kryger_1998_J.Physiol.Paris_92_191
PubMedID: 9789806

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Citations formats

Kryger G, Silman I, Sussman JL (1998)
Three-dimensional structure of a complex of E2020 with acetylcholinesterase from Torpedo californica
Journal de Physiologie Paris 92 :191

Kryger G, Silman I, Sussman JL (1998)
Journal de Physiologie Paris 92 :191