2c4h

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{{STRUCTURE_2c4h| PDB=2c4h | SCENE= }}
{{STRUCTURE_2c4h| PDB=2c4h | SCENE= }}
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'''TORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH 500MM ACETYLTHIOCHOLINE'''
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===TORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH 500MM ACETYLTHIOCHOLINE===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_16763558}}
==About this Structure==
==About this Structure==
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[[Category: Substrate-inhibition]]
[[Category: Substrate-inhibition]]
[[Category: Synapse]]
[[Category: Synapse]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 21:14:15 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 6 12:05:38 2008''

Revision as of 09:05, 6 July 2008

Image:2c4h.png

Template:STRUCTURE 2c4h

TORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH 500MM ACETYLTHIOCHOLINE

Template:ABSTRACT PUBMED 16763558

About this Structure

2C4H is a Single protein structure of sequence from Torpedo californica. Full crystallographic information is available from OCA.

Reference

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

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