1KU6

Fasciculin 2-Mouse Acetylcholinesterase Complex

Summary for 1KU6

• Entry DOI: 10.2210/pdb1ku6/pdb
• Related: 1mah
• Descriptor: ACETYLCHOLINESTERASE, FASCICULIN 2, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: hydrolase, serine esterase, synapse, venom, toxin, hydrolase-toxin complex, hydrolase/toxin
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 67461.16

Authors

Bourne, Y.,Burmeister, W.,Taylor, P.,Marchot, P. (deposition date: 2002-01-21, release date: 2003-12-23, Last modification date: 2024-10-30)

Primary citation

Bourne, Y.,Taylor, P.,Radic, Z.,Marchot, P.
Structural insights into ligand interactions at the acetylcholinesterase peripheral anionic site.
EMBO J., 22:1-12, 2003

PubMed Abstract: The peripheral anionic site on acetylcholinesterase (AChE), located at the active center gorge entry, encompasses overlapping binding sites for allosteric activators and inhibitors; yet, the molecular mechanisms coupling this site to the active center at the gorge base to modulate catalysis remain unclear. The peripheral site has also been proposed to be involved in heterologous protein associations occurring during synaptogenesis or upon neurodegeneration. A novel crystal form of mouse AChE, combined with spectrophotometric analyses of the crystals, enabled us to solve unique structures of AChE with a free peripheral site, and as three complexes with peripheral site inhibitors: the phenylphenanthridinium ligands, decidium and propidium, and the pyrogallol ligand, gallamine, at 2.20-2.35 A resolution. Comparison with structures of AChE complexes with the peptide fasciculin or with organic bifunctional inhibitors unveils new structural determinants contributing to ligand interactions at the peripheral site, and permits a detailed topographic delineation of this site. Hence, these structures provide templates for designing compounds directed to the enzyme surface that modulate specific surface interactions controlling catalytic activity and non-catalytic heterologous protein associations.

PubMed: 12505979
DOI: 10.1093/emboj/cdg005

Experimental method

X-RAY DIFFRACTION (2.5 Å)