2c5g: Difference between revisions

Revision as of 17:45, 21 February 2008

TORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH 20MM THIOCHOLINE

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

2C5G is a Single protein structure of sequence from Torpedo californica with , , and as ligands. Active as Acetylcholinesterase, with EC number 3.1.1.7 Known structural/functional Site: . 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 Thu Feb 21 16:45:05 2008

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OCA

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 ==Overview==
-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.
+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 Structure==
@@ Line 14: / Line 14: @@
 [[Category: Single protein]]
 [[Category: Torpedo californica]]
-[[Category: Colletier, J.P.]]
+[[Category: Colletier, J P.]]
 [[Category: Fournier, D.]]
-[[Category: Greenblatt, H.M.]]
+[[Category: Greenblatt, H M.]]
 [[Category: Silman, I.]]
-[[Category: Sussman, J.L.]]
+[[Category: Sussman, J L.]]
 [[Category: Weik, M.]]
 [[Category: Zaccai, G.]]
@@ Line 39: / Line 39: @@
 [[Category: synapse]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:31:42 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:45:05 2008''