1EVE

THREE DIMENSIONAL STRUCTURE OF THE ANTI-ALZHEIMER DRUG, E2020 (ARICEPT), COMPLEXED WITH ITS TARGET ACETYLCHOLINESTERASE

Summary for 1EVE

• Entry DOI: 10.2210/pdb1eve/pdb
• Descriptor: ACETYLCHOLINESTERASE, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: alzheimer's disease, drug, serine hydrolase, alpha/beta hydrolase, neurotransmitter cleavage, catalytic triad, glycosylated protein
• Biological source: Torpedo californica (Pacific electric ray)
• Cellular location: Isoform H: Cell membrane; Lipid-anchor, GPI- anchor. Isoform T: Cell membrane; Peripheral membrane protein: P04058
• Total number of polymer chains: 1
• Total formula weight: 62792.61

Authors

Kryger, G.,Silman, I.,Sussman, J.L. (deposition date: 1998-03-04, release date: 1999-01-20, Last modification date: 2024-10-23)

Primary citation

Kryger, G.,Silman, I.,Sussman, J.L.
Structure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti-Alzheimer drugs.
Structure Fold.Des., 7:297-307, 1999

PubMed Abstract: Several cholinesterase inhibitors are either being utilized for symptomatic treatment of Alzheimer's disease or are in advanced clinical trials. E2020, marketed as Aricept, is a member of a large family of N-benzylpiperidine-based acetylcholinesterase (AChE) inhibitors developed, synthesized and evaluated by the Eisai Company in Japan. These inhibitors were designed on the basis of QSAR studies, prior to elucidation of the three-dimensional structure of Torpedo californica AChE (TcAChE). It significantly enhances performance in animal models of cholinergic hypofunction and has a high affinity for AChE, binding to both electric eel and mouse AChE in the nanomolar range.

PubMed: 10368299
DOI: 10.1016/S0969-2126(99)80040-9

Experimental method

X-RAY DIFFRACTION (2.5 Å)