1n5m: Difference between revisions

Revision as of 02:07, 3 May 2008

Crystal structure of the mouse acetylcholinesterase-gallamine complex

OverviewOverview

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.

About this StructureAbout this Structure

1N5M is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

ReferenceReference

Structural insights into ligand interactions at the acetylcholinesterase peripheral anionic site., Bourne Y, Taylor P, Radic Z, Marchot P, EMBO J. 2003 Jan 2;22(1):1-12. PMID:12505979 Page seeded by OCA on Sat May 3 02:07:20 2008

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OCA

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 [[Image:1n5m.gif|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_1n5m", creates the "Structure Box" on the page.
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-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.7 3.1.1.7] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= ACHE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])
+-->
-|DOMAIN=
+{{STRUCTURE_1n5m|  PDB=1n5m  |  SCENE=  }}
-|RELATEDENTRY=[[1j06|1J06]], [[1j07|1J07]], [[1n5r|1N5R]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1n5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n5m OCA], [http://www.ebi.ac.uk/pdbsum/1n5m PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1n5m RCSB]</span>
-}}
 '''Crystal structure of the mouse acetylcholinesterase-gallamine complex'''
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 [[Category: Radic, Z.]]
 [[Category: Taylor, P.]]
-[[Category: acetylcholinesterase]]
+[[Category: Acetylcholinesterase]]
-[[Category: glycosylated protein]]
+[[Category: Glycosylated protein]]
-[[Category: homodimer]]
+[[Category: Homodimer]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: hydrolase fold]]
+[[Category: Hydrolase fold]]
-[[Category: serine esterase]]
+[[Category: Serine esterase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 02:07:20 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:25:41 2008''