2c58: Difference between revisions

Revision as of 21:16, 3 May 2008

TORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH 20MM ACETYLTHIOCHOLINE

OverviewOverview

Acetylcholinesterase (AChE) terminates nerve-impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter, acetylcholine. Substrate traffic in AChE involves at least two binding sites, the catalytic and peripheral anionic sites, which have been suggested to be allosterically related and involved in substrate inhibition. Here, we present the crystal structures of Torpedo californica AChE complexed with the substrate acetylthiocholine, the product thiocholine and a nonhydrolysable substrate analogue. These structures provide a series of static snapshots of the substrate en route to the active site and identify, for the first time, binding of substrate and product at both the peripheral and active sites. Furthermore, they provide structural insight into substrate inhibition in AChE at two different substrate concentrations. Our structural data indicate that substrate inhibition at moderate substrate concentration is due to choline exit being hindered by a substrate molecule bound at the peripheral site. At the higher concentration, substrate inhibition arises from prevention of exit of acetate due to binding of two substrate molecules within the active-site gorge.

About this StructureAbout this Structure

2C58 is a Single protein structure of sequence from Torpedo californica. Full crystallographic information is available from OCA.

ReferenceReference

Structural insights into substrate traffic and inhibition in acetylcholinesterase., Colletier JP, Fournier D, Greenblatt HM, Stojan J, Sussman JL, Zaccai G, Silman I, Weik M, EMBO J. 2006 Jun 21;25(12):2746-56. Epub 2006 Jun 8. PMID:16763558 Page seeded by OCA on Sat May 3 21:16:17 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:2c58.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2c58 |SIZE=350|CAPTION= <scene name='initialview01'>2c58</scene>, resolution 2.30&Aring;
+The line below this paragraph, containing "STRUCTURE_2c58", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Cl+Binding+Site+For+Chain+A'>AC1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=AT3:ACETYLTHIOCHOLINE'>AT3</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ETM:2-(TRIMETHYLAMMONIUM)ETHYL+THIOL'>ETM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OAS:O-ACETYLSERINE'>OAS</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|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=
+-->
-|DOMAIN=
+{{STRUCTURE_2c58|  PDB=2c58  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c58 OCA], [http://www.ebi.ac.uk/pdbsum/2c58 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2c58 RCSB]</span>
-}}
 '''TORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH 20MM ACETYLTHIOCHOLINE'''
@@ Line 33: / Line 30: @@
 [[Category: Weik, M.]]
 [[Category: Zaccai, G.]]
-[[Category: alpha/beta hydrolase]]
+[[Category: Alpha/beta hydrolase]]
-[[Category: alternative splicing]]
+[[Category: Alternative splicing]]
-[[Category: glycoprotein]]
+[[Category: Glycoprotein]]
-[[Category: gpi-anchor]]
+[[Category: Gpi-anchor]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: lipoprotein]]
+[[Category: Lipoprotein]]
-[[Category: membrane]]
+[[Category: Membrane]]
-[[Category: neurotransmitter cleavage]]
+[[Category: Neurotransmitter cleavage]]
-[[Category: neurotransmitter degradation]]
+[[Category: Neurotransmitter degradation]]
-[[Category: serine esterase]]
+[[Category: Serine esterase]]
-[[Category: substrate inhibition]]
+[[Category: Substrate inhibition]]
-[[Category: synapse]]
+[[Category: Synapse]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 21:16:17 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:16:30 2008''